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Vitreomacular interface abnormalities and glaucoma in an elderly population (the MONTRACHET study)
Julie Blanc, Alassane Seydou, Inès Ben Ghezala, Clémence Deschasse, Cyril Meillon, Alain M. Bron, Christine Binquet, Catherine Creuzot Garcher
To cite this version:
Julie Blanc, Alassane Seydou, Inès Ben Ghezala, Clémence Deschasse, Cyril Meillon, et al.. Vitreo- macular interface abnormalities and glaucoma in an elderly population (the MONTRACHET study).
Investigative Ophthalmology & Visual Science, Association for Research in Vision and Ophthalmology,
2019, 60 (6), pp.1996-2002. �10.1167/iovs.18-26510�. �hal-02620989�
Vitreomacular Interface Abnormalities and Glaucoma in an Elderly Population (The MONTRACHET Study)
Julie Blanc,
1Alassane Seydou,
2,3In` es Ben Ghezala,
1Cl´ emence Deschasse,
1Cyril Meillon,
1Alain M. Bron,
1,3Christine Binquet,
2,3and Catherine Creuzot-Garcher
1,31
University Hospital, Department of Ophthalmology, Dijon, France
2
Institut National de la Sant´ e et de la Recherche M´ edicale (INSERM), Clinical Center Investigation, Clinical Epidemiology/Clinical Trials Unit, Universal Hospital, Dijon, France
3
Centre des Sciences du Goˆ ut et de l’Alimentation, Centre National pour la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA), University Bourgogne Franche-Comt´ e, Dijon, France
Correspondence: Alain M. Bron, De- partment of Ophthalmology, Univer- sity Hospital, 14 rue Paul Gaffarel, Dijon 21079, France;
alain.bron@chu-dijon.fr.
Submitted: December 29, 2018 Accepted: April 9, 2019 Citation: Blanc J, Seydou A, Ben Ghezala I, et al. Vitreomacular inter- face abnormalities and glaucoma in an elderly population (the MONTRA- CHET Study).Invest Ophthalmol Vis Sci. 2019;60:1996–2002. https://
doi.org/10.1167/iovs.18-26510
P
URPOSE. To investigate the prevalence of vitreomacular interface abnormalities (VMIAs) in a French elderly glaucomatous population.
M
ETHODS. Using a population-based study, the MONTRACHET (Maculopathy Optic Nerve nuTRition neurovAsCular and HEarT diseases) study conducted in Dijon from 2009 to 2013 in individuals older than 75 years, the prevalence of VMIAs was estimated on glaucoma patients.
R
ESULTS. A total of 1130 participants (2225 eyes) were included in the study. The mean age of participants was 82.3 6 3.8 years, and 62.74% were women. Regarding the frequency of all VMIAs, there was no statistical difference between glaucoma patients and nonglaucoma participants (51.85% vs. 53.92%, respectively, P ¼ 0.372). In univariate analysis, vitreomacular adherences were more frequent in nonglaucoma participants (18.39% vs. 10.78%, P ¼ 0.036).
Epiretinal membranes were more frequent in the glaucomatous population (47.06% vs.
38.13%, P ¼ 0.018). The prevalence of macular cysts was comparable in the two groups (7.84% vs. 5.64%, P ¼ 0.262). Macular cysts were more frequent in eyes treated with preservative-free, IOP-lowering eye drops when compared with the eyes of nonglaucomatous participants treated with IOP-lowering eye drops containing a preservative (26.67% vs. 3.37%
and 5.76%, respectively, P < 0.001). In multivariate analysis, these results were no longer significant.
C
ONCLUSIONS. The prevalence of VMIAs was high in this elderly population and similar in both glaucomatous and nonglaucomatous participants. The information provided by macular optical coherence tomography scans should be considered with caution when used for glaucoma management in elderly patients.
Keywords: glaucoma, population-based study, spectral-domain optical coherence tomography, vitreomacular interface
T he emergence of optical coherence tomography (OCT) more than 2 decades ago has led to a dramatic improve- ment in visualizing and evaluating the vitreomacular interface and in diagnosing vitreomacular interface abnormalities (VMIAs). Recently, the International Vitreomacular Group described a new classification of VMIAs.1 Indeed, current or incomplete posterior vitreous detachment (PVD) has been shown to lead to vitreomacular adhesion or vitreomacular traction.
2Associations have also been described between PVD and epiretinal membranes.
2,3Posterior vitreous detachment is an age-related physiological event, with a high prevalence rate (around 80%) in the elderly population.
4,5Some reports suggest that intravitreal oxidative stress could disrupt hyaluronic acid levels, leading to vitreous liquefaction and ultimately PVD or in some cases VMIAs.
6In addition, the proliferation of glial cells, fibrous astrocytes, fibrocytes, and myofibroblasts contributes to the development of epiretinal membranes.
7
Glaucoma is a chronic ocular disorder characterized by the progressive loss of retinal ganglion cells. It is the leading cause of irreversible blindness, and some estimates predict that it will
affect about 112 million people worldwide by 2040.
8Several risk factors associated with glaucoma have been identified, such as family history, age, myopia, ethnicity, and elevated intraocular pressure (IOP), whereas others are still debated or remain unknown.
9Low-grade inflammation seems to play a crucial role in the pathogenesis of glaucoma, and in glaucoma- tous eyes, oxidative stress leads to an inflammatory response including microglial and complement activation as well as chemokine/cytokine production.
10–12For the diagnosis and follow-up of glaucoma, functional and structural tests are recommended.
13Optical coherence tomography for retinal nerve fiber layer (RNFL) measurements is the widely used test for documenting the structure of the optic nerve head.
However, recent studies have indicated that additional infor- mation can be gleaned from examining changes of the macular OCT scan, with the so-called ganglion cell complex (GCC).
14,15Some authors reported that GCC thickness seems to be more sensitive than the RNFL OCT scan to detect early glaucomatous damage
16,17or for monitoring eyes with advanced glaucoma.
18Conversely, some authors did not find any difference between
Copyright 2019 The Authors
iovs.arvojournals.orgjISSN: 1552-5783
1996
the yield of RNFL and GCC capability to differentiate normal and glaucomatous eyes.
19,20Nevertheless, VMIAs are a confounding factor for the conclusions that may be drawn from GCC.
21Therefore, we prompted this study to evaluate the prevalence and potential associations of VMIAs with glaucoma in an elderly population.
M
ATERIALS ANDM
ETHODSMONTRACHET Population
The MONTRACHET (Maculopathy Optic Nerve and nuTrition neurovAsCular and HEarT disease) Study was a prospective population-based study investigating the prevalence of age- related eye diseases and their relation with nutritional, environmental, and vascular factors. Participants were recruit- ed from an ongoing population-based study, the Three-City Study, which began in 1999 and was designed to examine the relationship between vascular diseases and dementia in 9294 community-dwelling persons aged older than 65 years.
22The participants were selected from the electoral rolls and were urban. They lived in one of the following three French cities:
Bordeaux, Dijon, or Montpellier. The MONTRACHET Study was an ancillary study conducted in Dijon and designed to estimate the frequency of eye diseases and the potential associations in individuals older than 75 years of age. The methodology of the MONTRACHET Study and the participant and nonparticipant characteristics have already been de- scribed.
22From October 2009 to March 2013, 1153 volunteers were included. The study was approved by the regional ethics committee and was registered as 2009-A00448-49. All partic- ipants gave their informed consent, and the study followed the tenets of the Declaration of Helsinki.
Eye Examination
Data were collected on lifestyle, environment, and medical history, including ophthalmic diseases and treatments. All participants underwent a complete eye examination in the Department of Ophthalmology at the Dijon University Hospital (France). The eye examination included IOP measurement with a noncontact tonometer (Tonoref II, Nidek, Gamagori, Japan), slit-lamp biomicroscopy, macular and optic disc photographs with a nonmydriatic camera (TRC-NW6S; Topcon, Tokyo, Japan), axial length measurement, central corneal thickness, and visual field measurement in screening (Frequen- cy-Doubling Technology, Carl Zeiss Meditec, Dublin, CA, USA).
Spectral-domain OCT (SD-OCT; software version 5.4.7.0;
Spectralis, Heidelberg Engineering Co., Heidelberg, Germany) was performed for both the macula and the optic nerve head after pupil dilation. The high-speed resolution mode and the eye-tracking system were activated to acquire the images. For the macula, an OCT image was obtained with a 208 3 158 pattern size, 19 B-scans spaced 235 lm apart, and the automatic real-time mode on. For the optic disc, the RNFL thickness acquisition was obtained with a circle diameter of 3.5 mm and 16 images with the automatic real-time function.
The system automatically calculated the RNFL thickness globally and according to six segments (the superotemporal, temporal, inferotemporal, inferonasal, nasal, and superonasal segments).
Main Outcome Parameters
The presence of VMIAs was determined using SD-OCT and based on the macular cube. Vitreomacular adherences, vitreomacular tractions, and macular holes were analyzed and
classified according to the International Vitreomacular Group classification
1(Fig. 1). Epiretinal membranes and macular cysts were also studied (Fig. 1). Vitreomacular adherence was defined as evidence of perifoveal vitreous cortex detachment from the retinal surface, macular attachment of the vitreous cortex within a 3-mm radius of the fovea, and no detectable change in foveal contour or underlying retinal tissues.
1Vitreomacular traction was defined as evidence of perifoveal vitreous cortex detachment from the retinal surface, macular attachment of the vitreous cortex within a 3-mm radius of the fovea, and attachment associated with distortion of the foveal surface, intraretinal structural changes, and/or elevation of the fovea above the retinal pigment epithelium, but no full- thickness interruption of all retinal layers.
1A lamellar macular hole was defined as irregular foveal contour; defect in the inner fovea; intraretinal splitting (schisis), typically between the outer plexiform and outer nuclear layers, and preservation of an intact photoreceptor layer.
1A full-thickness macular hole was defined as a full-thickness foveal lesion that interrupts all macular layers from the internal limiting membrane to the
FIGURE1. Classification of vitreomacular interface abnormalities using macular spectral-domain optical coherence tomography: (A) vitreo- macular adhesion, (B) vitreomacular traction, (C) lamellar macular hole, (D) full-thickness macular hole, (E) macular pseudohole, (F) epiretinal membrane, (G) macular cysts.VMIAS and Glaucoma in the Elderly IOVS j May 2019 j Vol. 60 j No. 6 j 1997
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retinal pigment epithelium.
1A macular pseudohole was defined as invaginated or heaped foveal edges, concomitant epiretinal membrane with central opening and steep macular contour to the central fovea with near-normal central foveal thickness, and no loss of retinal tissue.
1As there is no international consensus, epiretinal membranes were defined as hyper-reflectivity along the surface of the internal limiting membrane.
23Macular cysts were defined as hyporeflective spaces with well-defined margins within the retina. A cyst was considered definitely present if it was visible in at least two consecutive B-scans and was larger than 15 lm in vertical diameter.
23Definition of Glaucoma
Eyes were diagnosed with glaucoma as defined by the International Society for Geographical and Epidemiological Ophthalmology.
24Identified glaucoma eyes were reexamined with gonioscopy and a Humphrey Swedish Interactive Thresh- olding Algorithm 24-2 visual field (Carl Zeiss Meditec, Dublin, CA, USA). Optic disc photographs were interpreted in duplicate by two ophthalmologists. In case of discrepancy, the adjudication was made by a glaucoma specialist. For determining the three levels of evidence described by Foster et al,
24we used the 97.5th and 99.5th percentiles for the vertical cup-to-disk-ratio found in our population-based study. The 97.5 and 99.5 percentiles for the vertical cup-to-disk-ratio and vertical cup-to-disk-ratio asymmetry were 0.7, 0.2 and 0.8, 0.3, respectively.
Statistical Analysis
Categorical variables were expressed as n (%), and continuous variables using mean 6 SD because the distribution of continuous variables was normal according to the Shapiro test. For the comparison between nonglaucoma and glaucoma participants, we used generalized estimating equation regres- sion models to take into account intraindividual correlations between the two eyes. Only associations of vitreomacular adherences, epiretinal membranes, and macular cysts with age, sex, smoking, alcohol, diabetes, ocular hypertension, cataract extraction, and axial length were estimated because they were the most prevalent.
Model A consisted of patients diagnosed with glaucoma according to the International Society for Geographical and Epidemiological Ophthalmology criteria. Model B consisted of patients who declared taking IOP-lowering eye drops. Multi- variate analysis was estimated after adjustment for age, sex, cataract extraction, and axial length (with a P value < 0.10).
Associations were presented as odds ratio (OR) and confidence interval (95% CI). For all tests, P values < 0.05 were considered statistically significant. All statistical analyses were performed using SAS statistical software (version 9.4; SAS Institute, Inc., Cary, NC, USA).
R
ESULTSOverall, 1130 (2225 eyes) of the 1153 participants of the MONTRACHET Study with at least one available and interpret- able OCT scan were included in the study (Fig. 2). The baseline demographics and clinical characteristics of participants and nonparticipants are shown in Supplementary Table 1. Nonpar- ticipants were more likely to have a longer axial length than participants (P < 0.001). The classification of glaucoma cases was as follows: 89 primary open-angle glaucomas, 2 primary angle closure glaucomas, and 11 secondary glaucomas. For primary open-angle glaucomas, the level of evidence according
to Foster was n ¼ 56 for category 1 diagnosis, n ¼ 32 for category 2 diagnosis, and n ¼ 1 for category 3 diagnosis.
24The frequency of VMIAs in the entire population was 52.04%. Of these, the most frequent VMIAs were epiretinal membranes (38.94%), vitreomacular adherences (17.70%), and macular cysts (5.84%). In multivariate analysis taking age, sex, smoking, alcohol, diabetes, ocular hypertension, cataract extraction, and axial length into account, an increased likelihood of both vitreomacular adherences and epiretinal membranes was significantly associated with male gender, cataract extraction, and axial length (P < 0.01 for each factor, respectively).
Vitreomacular adherences were significantly associated with younger age (P < 0.01), whereas epiretinal membranes were associated with older age (P < 0.01). Lastly, macular cysts were also significantly associated with older age (P ¼ 0.04), male gender (P ¼ 0.01), cataract extraction (P < 0.01), and axial length (P ¼ 0.04).
Model A
Among the 1130 participants, 102 patients (176 eyes) were diagnosed with glaucoma and included in Model A. The baseline demographics and clinical characteristics of these participants are shown in Table 1. In univariate analysis, regarding the frequency of all VMIAs, there was no statistical difference between the glaucoma group and controls (51.85%
vs. 53.92%, respectively, P ¼ 0.372). However, the frequency of epiretinal membranes was statistically higher in the glaucoma group (47.06% vs. 38.13%, P ¼ 0.018), whereas vitreomacular adherences were significantly less frequent (10.78% vs.
18.39%, P ¼ 0.036; Table 2). In multivariate analysis adjusted on age, sex, cataract extraction, and axial length, those correlations were no longer significant (Table 3).
Model B
Among the 1130 participants, 106 patients (212 eyes) treated with IOP-lowering eye drops were included in Model B.
Treatments and therapeutic classes are detailed in Supplemen-
tary Table 2. In univariate analysis, the frequency of epiretinal
membranes was similar in both groups receiving IOP-lowering
eye drops when compared with control (OR [95% CI] ¼ 1.42
[0.95–2.11], P ¼ 0.083 and OR [95% CI] ¼ 1.47 [0.58–3.75], P ¼
FIGURE2. Workflow of the study.0.417 for preservative and preservative-free groups, respec- tively) as well as for vitreomacular adherences (OR [95% CI] ¼ 0.61 [0.31–1.18], P ¼ 0.139 and OR [95% CI] ¼ 1.42 [0.39–
5.15], P ¼ 0.585 for preservative and preservative-free groups, respectively). For macular cysts, the frequency was higher in both groups when compared with controls, but it was only significant for the group with preservative-free, IOP-lowering eye drops (26.67% vs. 5.22%, P < 0.001; Table 4). In multivariate analysis adjusted on age, sex, cataract extraction, and axial length, those correlations were no longer statistically significant. More detailed results of the multivariate analysis for Model B are presented in Table 3.
D
ISCUSSIONThis study was designed with the major objective of evaluating the association between glaucoma and VMIAs. To our knowledge, the association between VMIAs and glaucoma has not yet been reported in the literature. Although we found no differences in terms of prevalence for glaucoma and nonglaucoma eyes in VMIAs as a whole, our results contribute relevant information regarding each of the three major VMIAs (vitreomacular adherences, epiretinal membranes, macular cysts) independently.
In univariate analysis, we found a lower prevalence of vitreomacular adherences in the glaucoma group (10.78%) when compared with controls (18.39%; P ¼ 0.036). However, in multivariate analysis the results were no longer significant (OR [95% CI] ¼ 0.81 [0.41–1.59], P ¼ 0.536). In the Beijing Eye Study, incomplete PVD was defined as a persistent perifoveolar attachment, close to our definition of vitreomacular adherenc- es.
25The findings reported here were congruent with this
study as the authors found an association between incomplete PVD and younger age, male gender, and hyperopic refractive error.
25Several studies investigated the prevalence and risk factors of PVD in a healthy population.
4,26One of them reported a prevalence of 18.5% of foveal adhesion, which is comparable with our data for nonglaucomatous eyes.
4Schwab et al.
27evaluated the prevalence of PVD in glaucoma patients.
The authors observed that PVD was more prevalent in patients with glaucoma when compared with nonglaucomatous partic- ipants.
27One possible explanation is that the increased oxidative stress in patients with glaucoma may lead to vitreous changes taking into consideration the proximity between the retinal ganglion cells and the vitreous.
10,11,28In contrast, a recent study found that glaucoma patients experienced PVD formation at an older age when compared with healthy individuals but reached complete PVD at a similar age. They suggested that the optic disc may remain exposed to possible vitreous traction longer in glaucoma patients than in healthy individuals because of stronger vitreoretinal adhesion.
29Regarding epiretinal membranes, with univariate analysis, we found a higher prevalence in glaucoma eyes (47.06%) than in nonglaucoma eyes (38.13%; P ¼ 0.018). However, as for vitreomacular adherences, this was no longer significant in multivariate analysis (OR [95% CI] ¼ 1.40 [0.91–2.15], P ¼ 0.120). Several population-based studies have documented the prevalence of epiretinal membranes with rates ranging from 2.2% to 34.1%.
23,30–33The disparity between studies stems from the several methods of epiretinal membrane assessment used, including some studies that used only fundus photo- graphs.
30–33The higher prevalence found in our study is closer to the Beaver Dam Study, which used SD-OCT as well.
23A recent retrospective case-series study reported an association
TABLE1. Baseline Characteristics of Participants, the MONTRACHET Study*Variables Total,N¼1130
Glaucoma
OR (95% CI) P
No,n¼1028 Yes,n¼102 Age, y
<80 390 (34.51) 366 (35.60) 24 (23.53) 1.00 (reference)
80–85 477 (42.21) 438 (42.61) 39 (38.24) 1.36 (0.80–2.30) 0.255
>85 263 (23.27) 224 (21.79) 39 (38.24) 2.65 (1.55–4.53) <0.001
Sex, male 421 (37.26) 375 (36.48) 46 (45.10) 1.43 (0.95–2.15) 0.087
Smoking status, yes 383 (34.47) 343 (33.89) 40 (40.40) 1.32 (0.87–2.02) 0.194
Alcohol consumption, yes 63 (6.30) 57 (6.27) 6 (6.59) 1.05 (0.44–2.52) 0.905
Diabetes, yes 92 (9.21) 81 (8.92) 11 (12.09) 1.40 (0.72–2.74) 0.321
IOP>21 mm Hg 80 (7.08) 70 (6.81) 10 (9.80) 1.49 (0.74–2.98) 0.263
Cataract extraction, yes 553 (49.07) 485 (47.32) 68 (66.67) 2.23 (1.45–3.42) <0.001
Axial length, mm 23.4261.30 23.3761.27 23.8961.56 1.02 (0.99–1.05) 0.094
* Missing data for smoking (n¼19), alcohol (n¼130), diabetes (n¼131), cataract extraction (n¼3), and axial length (n¼194). Results are displayed as number (percentages) for categorical variables and mean6standard deviation for continuous variables.
TABLE2. Prevalence of Vitreomacular Interface Abnormalities in Model A, the MONTRACHET Study, Univariate Analysis*
Vitreomacular Interface Abnormalities
Nonglaucoma Participants, n¼1028
Glaucoma Patients,
n¼102 OR (95% CI) P
Vitreomacular adherences 189 (18.39) 11 (10.78) 0.49 (0.26–0.96) 0.036
Vitreomacular tractions 16 (1.56) 0 (0.0)
Lamellar macular holes 9 (0.86) 2 (1.96) 1.85 (0.39–8.72) 0.435
Full-thickness macular holes 2 (0.19) 0 (0.0)
Macular pseudoholes 3 (0.29) 1 (0.98)
Epiretinal membranes 392 (38.13) 48 (47.06) 1.57 (1.08–2.29) 0.018
Macular cysts 58 (5.64) 8 (7.84) 1.56 (0.72–3.39) 0.262
All vitreomacular interface abnormalities 533 (51.85) 55 (53.92) 1.18 (0.82–1.69) 0.372
* Results are displayed as number (percentages) for categorical variables.
VMIAS and Glaucoma in the Elderly IOVS j May 2019 j Vol. 60 j No. 6 j 1999
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with epiretinal membranes and the severity of glaucoma.
34We are not aware of any previous studies investigating the frequency of epiretinal membranes in a glaucoma population in the frame of a population-based study. However, a very recent case-control study reported a higher prevalence of epiretinal membranes in early glaucoma.
35We hypothesized that the overactivation of glial cells in glaucomatous eyes could lead to the formation of epiretinal membranes. Indeed, activated glial cells have been well documented in experimen- tal glaucoma models.
36–38Recently, microglial and M¨ uller cells were identified in an in vitro culture of human epiretinal membranes, supporting the involvement of glial cells in both diseases.
39For macular cysts, the prevalence was similar between the glaucoma group and controls. Indeed, even if microcystic macular changes in the inner nuclear layer of glaucomatous eyes have been described in the literature, this is not pathognomonic for glaucoma.
40We also found a higher prevalence of macular cysts in eyes treated with preservative- free, IOP-lowering eye drops (26.67%) versus 3.37% and 5.84% in eyes treated with IOP-lowering eye drops containing preservatives and in the entire population, respectively. One explanation could be the lower frequency of individuals receiving carbonic anhydrase inhibitors in the group treated with preservative-free, IOP-lowering eye drops (13.33%) when compared with the group treated with preservative IOP-lowering eye drops (22.47%). Indeed, it has been demonstrated that carbonic anhydrase inhibitors were useful for the treatment of macular edema, especially when taken orally.
41–43Recently, topical treatment also showed efficacy for macular edema in patients diagnosed with retinitis pigmentosa.
44,45Nevertheless, although this may explain the difference between the two groups, it still does not elucidate the high rate of macular cysts in the preservative- free, IOP-lowering eye drops group. Also, most of these preservative eye drops contain benzalkonium chloride, which is known to damage the tear film and corneal surface by inducing oxidative stress and inflammation
46–50or even impact tissues inside the eye. Yet, we were not able to
confirm the potential involvement of benzalkonium chloride in the development of VMIAs. Indeed, our results should be interpreted with caution considering the uneven number of eyes in the two groups and particularly the small number of eyes treated with preservative-free, IOP-lowering eye drops.
In our old cohort, a macular OCT scan revealed a VMIA in more than half of the glaucomatous population. These findings challenge the current reports on the systematic use of GCC thickness analysis on the macular OCT scan for diagnosing or monitoring glaucomatous damage.
21Indeed, previous studies have already described GCC changes in several retinal diseases, such as diabetic retinopathy
51and AMD.
52,53The GCC was analyzed using automatic segmentation without checking the accuracy of delineation of segmented retinal layers, explaining the high error rate. Recently, Muftuoglu et al.
54also reported GCC changes in patients with severe dry AMD even using the manual correction of segmentation.
One of the strengths of this study was its prospective design on a large elderly population. It also uses well-accepted definitions of both glaucoma and VMIAs.
1,24The first limitation is that we included an uneven number of participants in the two groups because there were not many patients diagnosed with glaucoma or treated with IOP-lowering eye drops.
Second, some data regarding lifestyle, environment, and medical history were based only on self-declaration, which may lead to information bias. Third, this study only examined a white, urban European population; therefore, the results cannot be extrapolated to other groups. Fourth, we could not analyze the GCC on the macular OCT scans of our cohort because automatic software for that purpose was not available at this time on the Spectralis SD-OCT.
In conclusion, the frequency of VMIAs was high in this elderly population in both glaucoma and nonglaucoma eyes.
Therefore, macular OCT is a fundamental tool for the follow-up of glaucomatous patients not only for GCC thickness evalua- tion but also for the early detection of VMIAs. In addition, we could not identify any statistically significant association between glaucoma and VMIAs when using multivariate analysis. Considering the high prevalence rate of VMIAs in an
TABLE4. Prevalence of Vitreomacular Interface Abnormalities in Model B, the MONTRACHET Study, Univariate Analysis*
Vitreomacular Interface Abnormalities
Model B,n¼106 Preservative,
n¼89;n(%) OR (95% CI) P
Preservative Free,
n¼15;n(%) OR (95% CI) P Vitreomacular adherences 11 (12.36) 0.61 (0.31–1.18) 0.139 3 (20.00) 1.42 (0.39–5.15) 0.585
Vitreomacular tractions 1 (1.12) 0
Lamellar macular holes 1 (1.12) 1 (6.67)
Full-thickness macular holes 0 0
Macular pseudoholes 1 (1.12) 0
Epiretinal membranes 41 (46.07) 1.42 (0.95–2.11) 0.083 7 (46.67) 1.47 (0.58–3.75) 0.417
Macular cysts 3 (3.37) 0.53 (0.16–1.68) 0.282 4 (26.67) 6.92 (2.27–21.09) <0.001
All vitreomacular interface abnormalities 47 (52.81) 1.10 (0.75–1.61) 0.631 10 (66.67) 2.08 (0.83–5.19) 0.116
* Results are displayed as number (percentages) for categorical variables.
TABLE3. Vitreomacular Abnormalities in the MONTRACHET Study, Multivariate Analysis
Vitreomacular Adherences Epiretinal Membranes Macular Cysts
OR (95% CI) P OR (95% CI) P OR (95% CI) P
Model A 0.81 (0.41–1.59) 0.536 1.40 (0.91–2.15) 0.120 0.78 (0.31–1.96) 0.596
Model B
Preservative 0.84 (0.43–1.63) 0.605 1.31 (0.87–1.98) 0.198 0.56 (0.18–1.78) 0.329
Preservative free 2.59 (0.82–8.25) 0.106 1.15 (0.39–3.91) 0.823 1.82 (0.26–12.61) 0.544
elderly population, this study warns macular OCT users that GCC should be interpreted with caution in elderly glaucoma- tous patients.
Acknowledgments
Supported by an interregional grant titled
‘‘Programme Hospitalierde Recherche Clinique’’ and the regional Council of Burgundy. All procedures performed in the studies involving human participants were in accordance with the ethical standards of the regional ethics committee (2009-A00448-49) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Disclosure:
J. Blanc, None; A. Seydou, None; I. Ben Ghezala,None;
C. Deschasse, None; C. Meillon, None; A.M. Bron,Allergan (C), Baush and Lomb (C), Santen Pharmaceutical (C), Th´ ea (C);
C. Binquet, None;C. Creuzot-Garcher, Allergan (C),Baush and Lomb (C), Novartis (C), Th´ ea (C)
References
1. Duker JS, Kaiser PK, Binder S, et al. The International Vitreomacular Traction Study Group classification of vitre- omacular adhesion, traction, and macular hole. Ophthalmol- ogy. 2013;120:2611–2619.
2. Johnson MW. Posterior vitreous detachment: evolution and complications of its early stages. Am J Ophthalmol. 2010;149:
371–382.
3. Koizumi H, Spaide RF, Fisher YL, Freund KB, Klancnik JM Jr, Yannuzzi LA. Three-dimensional evaluation of vitreomacular traction and epiretinal membrane using spectral-domain optical coherence tomography. Am J Ophthalmol. 2008;
145:509–517.
4. Schwab C, Ivastinovic D, Borkenstein A, Lackner EM, Wedrich A, Velikay-Parel M. Prevalence of early and late stages of physiologic PVD in emmetropic elderly population. Acta Ophthalmol. 2012;90:e179–e184.
5. Uchino E, Uemura A, Ohba N. Initial stages of posterior vitreous detachment in healthy eyes of older persons evaluated by optical coherence tomography. Arch Ophthal- mol. 2001;119:1475–1479.
6. Le Goff MM, Bishop PN. Adult vitreous structure and postnatal changes. Eye (Lond). 2008;22:1214–1222.
7. Hiscott PS, Grierson I, Trombetta CJ, Rahi AH, Marshall J, McLeod D. Retinal and epiretinal glia—an immunohistochem- ical study. Br J Ophthalmol. 1984;68:698–707.
8. Tham YC, Li X, Wong TY, Quigley HA, Aung T, Cheng CY.
Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis.
Ophthalmology. 2014;121:2081–2090.
9. Jonas JB, Aung T, Bourne RR, Bron AM, Ritch R, Panda-Jonas S.
Glaucoma. Lancet. 2017;390:2183–2193.
10. Xu H, Chen M, Forrester JV. Para-inflammation in the aging retina. Prog Retin Eye Res. 2009;28:348–368.
11. Vohra R, Tsai JC, Kolko M. The role of inflammation in the pathogenesis of glaucoma. Surv Ophthalmol. 2013;58:311–
320.
12. Tezel G. Oxidative stress in glaucomatous neurodegeneration:
mechanisms and consequences. Prog Retin Eye Res. 2006;25:
490–513.
13. European Glaucoma Society. Terminology and Guidelines for Glaucoma. 4th ed. Savona, Italy: SvetPrint d.o.o.; 2014.
14. Hood DC, Raza AS, de Moraes CG, Liebmann JM, Ritch R.
Glaucomatous damage of the macula. Prog Retin Eye Res.
2013;32:1–21.
15. Hood DC. Improving our understanding, and detection, of glaucomatous damage: an approach based upon optical
coherence tomography (OCT). Prog Retin Eye Res. 2017;57:
46–75.
16. Hood DC, Slobodnick A, Raza AS, de Moraes CG, Teng CC, Ritch R. Early glaucoma involves both deep local, and shallow widespread, retinal nerve fiber damage of the macular region.
Invest Ophthalmol Vis Sci. 2014;55:632–649.
17. Tan O, Chopra V, Lu AT, et al. Detection of macular ganglion cell loss in glaucoma by Fourier-domain optical coherence tomography. Ophthalmology. 2009;116:2305–2314.
18. Bowd C, Zangwill LM, Weinreb RN, Medeiros FA, Belghith A.
Estimating optical coherence tomography structural measure- ment floors to improve detection of progression in advanced glaucoma. Am J Ophthalmol. 2017;175:37–44.
19. Oddone F, Lucenteforte E, Michelessi M, et al. Macular versus retinal nerve fiber layer parameters for diagnosing manifest glaucoma: a systematic review of diagnostic accuracy studies.
Ophthalmology. 2016;123:939–949.
20. Pazos M, Dyrda AA, Biarnes M, et al. Diagnostic accuracy of spectralis SD OCT automated macular layers segmentation to discriminate normal from early glaucomatous eyes. Ophthal- mology . 2017;124:1218–1228.
21. Hood DC, De Moraes CG. Challenges to the common clinical paradigm for diagnosis of glaucomatous damage with OCT and visual fields. Invest Ophthalmol Vis Sci. 2018;59:788–
791.
22. Creuzot-Garcher C, Binquet C, Daniel S, et al. The Montrachet Study: study design, methodology and analysis of visual acuity and refractive errors in an elderly population. Acta Oph- thalmol. 2016;94:e90–e97.
23. Meuer SM, Myers CE, Klein BE, et al. The epidemiology of vitreoretinal interface abnormalities as detected by spectral- domain optical coherence tomography: the Beaver Dam Eye Study. Ophthalmology. 2015;122:787–795.
24. Foster PJ, Buhrmann R, Quigley HA, Johnson GJ. The definition and classification of glaucoma in prevalence surveys. Br J Ophthalmol. 2002;86:238–242.
25. Shao L, Xu L, You QS, et al. Prevalence and associations of incomplete posterior vitreous detachment in adult Chinese:
the Beijing Eye Study. PLoS One. 2013;8:e58498.
26. Chuo JY, Lee TY, Hollands H, et al. Risk factors for posterior vitreous detachment: a case-control study. Am J Ophthalmol.
2006;142:931–937.
27. Schwab C, Glatz W, Schmidt B, et al. Prevalence of posterior vitreous detachment in glaucoma patients and controls. Acta Ophthalmol. 2017;95:276–280.
28. Noristani R, Kuehn S, Stute G, et al. Retinal and optic nerve damage is associated with early glial responses in an experimental autoimmune glaucoma model. J Mol Neurosci.
2016;58:470–482.
29. Willekens K, Abegao Pinto L, Lemmens S, et al. The vitreopapillary interface in healthy and glaucoma: posterior vitreous detachment in the vitreopapillary interface study.
Acta Ophthalmol. 2018;96:573–581.
30. Aung KZ, Makeyeva G, Adams MK, et al. The prevalence and risk factors of epiretinal membranes: the Melbourne Collab- orative Cohort Study. Retina. 2013;33:1026–1034.
31. You Q, Xu L, Jonas JB. Prevalence and associations of epiretinal membranes in adult Chinese: the Beijing Eye Study.
Eye (Lond). 2008;22:874–879.
32. Ng CH, Cheung N, Wang JJ, et al. Prevalence and risk factors for epiretinal membranes in a multi-ethnic United States population. Ophthalmology. 2011;118:694–699.
33. Fraser-Bell S, Ying-Lai M, Klein R, Varma R, Los Angeles Latino Eye Study. Prevalence and associations of epiretinal mem- branes in latinos: the Los Angeles Latino Eye Study. Invest Ophthalmol Vis Sci. 2004;45:1732–1736.
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