Lamellar macular hole (LMH) is a retinal pathology characterized by a morphologic alteration of the structure of the fovea, which could lead to metamorphopsia and a reduction in best-corrected visual acuity (BCVA) [
Spectral-domain OCT (SD-OCT) provides an excellent visualization of the retinal structure and retinal layers [
Recently, the International Vitreomacular Study Group suggested optical coherence tomography (OCT) features to identify LMHs: defect in inner fovea; irregular foveal contour; intraretinal schisis; and preservation of the ellipsoid zone (EZ). The pathogenesis of LMHs still has to be fully understood, as well as its indication for surgical treatment [
Microperimetry is used to test sensitivity to light stimulus, with a precise point-to-point analysis. An eye-tracking system is used to correct noncentral fixation, and an infrared fundus image is constantly and simultaneously provided along the light sensitivity test. Microperimetry is of particular importance to assess the functional status of the macula in those pathologies characterized by subclinical symptoms, such as LMHs [
The aim of our study was to evaluate the association between visual function and anatomical characteristics of LMH, considering in particular different subtypes of LMH and their features.
In this observational cross-sectional study, we included consecutive patients with a diagnosis of an LMH examined at the Vitreoretinal Outpatient Service, Ophthalmology Clinic, University of Insubria of Varese, Italy, between September 2017 and July 2018.
An LMH was diagnosed based on SD-OCT characteristics as proposed by Witkin and as classified by Duker [
SD-OCT evaluation of tractional (a) and degenerative (b) lamellar macular hole.
Exclusion criteria were as follows: (1) the presence of myopia of more than three diopters in the affected eye (axial length more than 25 mm if pseudophakic eyes); (2) retinal pathologies that could influence a correct diagnosis or functional evaluation, such as age-related macular degeneration (AMD), diabetic retinopathy or retinal vascular occlusion; (3) vitreous hemorrhage; (4) cataract graded more than N03 or NC3, according to the Lens Opacity Classification System; (5) ocular surgery other than uncomplicated cataract surgery. Patients presenting low-quality SD-OCT imaging or unable to perform microperimetry evaluation due to weak cooperation were excluded.
All subjects underwent a complete ophthalmologic examination along with intraocular pressure measurement. Instrumental examination included microperimetry, and SD-OCT evaluation. Our study followed the methods published on Reibaldi et al. [
All subjects signed an informed consent for clinical examination and data management. Hospital ethical committee considered all clinical procedures as standard evaluation not requiring specifically intended approval.
BCVA was measured by Snellen charts and then converted to LogMAR for statistical analysis.
An MP-1 microperimeter (Nidek Technologies, Padua, Italy) was used to test retinal sensitivity and fixation. After the pupils were dilated (1% tropicamide), a reference frame was obtained with the integrated infrared camera. We used a 4-2-2 double-staircase test strategy with white background illumination set at 4 apostilbs and a starting stimulus light attenuation set at 10 dB. A grid of 45 stimuli with a Goldmann III stimulus size and a time between the stimuli of 1 s was projected onto the central 8° (Figure
Fundus color picture with retinal sensitivity grid.
The mean retinal sensitivity (total sensitivity, mTRS) and the mean sensitivity of the central 13 points within 2° (mean central sensitivity, mCRS) were calculated. The fixation pattern was evaluated as fixation stability and fixation location. Fixation stability was divided into three categories: stable, relatively unstable, or unstable. If 75% of fixation points were located within a two-degree diameter circle, regardless of their position in relation to the foveal center, the fixation was classified as stable. If 75% of fixation points were located within a two-degree circle, but 75% of fixation points were located within a four-degree circle, the fixation was classified as relatively unstable. If 75% of fixation points were located within a four-degree circle, the fixation was classified as unstable. Fixation location was divided into three categories: central, pericentral, and eccentric. If 50% of fixation points were within 0.5 mm of the foveal center, the fixation was classified as central. If 25% to 50% of the fixation points were within 0.5 mm of the foveal center, the fixation was classified as pericentral. If 25% of fixation points were within 0.5 mm of the foveal center, the fixation was classified as eccentric (as in the work of Donati et al. [
To rule out potential learning effects, all patients performed a preliminary test microperimetry examination. All imaging sessions were performed after 5 min of visual adaptation. The same experienced ophthalmologists carried out the examinations (P.D.; L.L.).
SD-OCT images were obtained with a Zeiss Cirrus HD OCT 500 version 7.0.1.290 (Carl Zeiss Meditec, Jena, Germany). All OCT examinations were carried out by a certified operator (S.D., CORC certification 2017). According to the protocol, OCT macular cube 512 × 128 and five-line scans, centered on the fovea, were obtained for each eye. More than 15 scans were averaged for each measurement. Only images with a quality score of more than five were selected as high-quality images.
According to the morphology of the LMH, all included eyes were divided into two subgroups based on the classification published by Govetto et al. [
OCT Morphological parameters analyzed in tractional (3.1) and degenerative LMH (3.2): horizontal diameter (A); central foveal thickness (B); depth of LMH (C); base diameter (D).
The following dimensional parameters of LMHs were measured in
Continuous variables were summarized using the sample median and the interquartile range due to the low number of observations and the skewed distribution of most parameters. Stable fixation and predominantly central fixation were dichotomized as yes vs. no and summarized using absolute and relative frequencies. To test the null hypothesis of no difference in functional and morphological parameters between the patients’ populations with tractional and degenerative LMH, we used the Wilcoxon rank test and Fisher’s exact test for continuous and dichotomic variables, respectively. We adopted the same descriptive and inferential approaches to investigate differences in patients’ populations defined according to the presence of interruptions in the ELM and IZ-EZ segment. All the analyses were conducted using the SAS software, 9.4 release.
Twenty-five eyes affected by an LMH were evaluated: of these, seven eyes were excluded (three due to the presence of concomitant macular diseases, two due to excessive refractive error, one due to a significant cataract, and one due to previous vitreoretinal surgery). Therefore, 18 eyes of 18 patients met the study inclusion criteria and were enrolled. Demographic and main clinical characteristics of the enrolled patients are reported in Table
Demographics and main clinical data of enrolled patients.
Patient | Age | Study eye | Funduscopic examination | Visual acuity | ||
---|---|---|---|---|---|---|
Study eye | Fellow eye | SE | FE | |||
1 | 70 | RE | Degenerative lamellar macular hole | No abnormalities | 0 | 0 |
2 | 68 | LE | Degenerative lamellar macular hole | Macular pucker | 0.09 | 0.3 |
3 | 75 | RE | Tractional lamellar macular hole | Previous surgery for macular hole | 0 | 0.6 |
4 | 71 | LE | Degenerative lamellar macular hole | Previous surgery for macular pucker | 0.5 | 0.6 |
5 | 73 | RE | Tractional lamellar macular hole | Macular membrane | 0 | 0 |
6 | 82 | RE | Degenerative lamellar macular hole | Previous surgery for macular hole | 0.15 | 0.6 |
7 | 72 | RE | Tractional lamellar macular hole | VMT | 0 | 0 |
8 | 68 | LE | Tractional lamellar macular hole | No abnormalities | 0 | 0 |
9 | 68 | LE | Tractional lamellar macular hole | No abnormalities | 0 | 0 |
10 | 67 | RE | Tractional lamellar macular hole | No abnormalities | 0.15 | 0.09 |
11 | 76 | LE | Degenerative lamellar macular hole | No abnormalities | 0.09 | 0.04 |
12 | 63 | RE | Tractional lamellar macular hole | Macula pucker | 0.15 | 0 |
13 | 71 | RE | Degenerative lamellar macular hole | No abnormalities | 0.5 | 0.15 |
14 | 78 | LE | Degenerative lamellar macular hole | Macular pucker | 0.15 | 0.6 |
15 | 77 | RE | Tractional lamellar macular hole | No abnormalities | 0.09 | 0.15 |
16 | 74 | RE | Tractional lamellar macular hole | Retinal vein occlusion | 0 | 0.04 |
17 | 80 | LE | Tractional lamellar macular hole | No abnormalities | 0.09 | 0.04 |
18 | 76 | RE | Tractional lamellar macular hole | No abnormalities | 0.04 | 0.04 |
Age: years; RE: right eye; LE: left eye; VMT: vitreomacular traction; SE: study eye; FE: fellow eye.
In Table
Morphological and functional data for both studied groups.
Patient | Age | BCVA | mCRS | mTRS | LMH depth | LMH base | LMH diameter | CFT | Integrity ELM | Integrity IZ-EZ | Fixation stability | Fixation status |
---|---|---|---|---|---|---|---|---|---|---|---|---|
|
||||||||||||
1 | 75 | 0.00 | 17.90 | 15.85 | 287 | 844 | 537 | 186 | + | + | Stable | Predominant central |
2 | 73 | 0.00 | 16.21 | 16.67 | 310 | 1325 | 650 | 193 | + | + | Relatively instable | Predominant central |
3 | 72 | 0.00 | 14.21 | 13.82 | 202 | 1280 | 601 | 165 | + | + | Instable | Poorly central |
4 | 68 | 0.00 | 15.75 | 16.30 | 278 | 560 | 410 | 170 | + | + | Stable | Predominant central |
5 | 68 | 0.00 | 16.62 | 15.50 | 205 | 672 | 200 | 232 | + | + | Stable | Predominant central |
6 | 67 | 0.15 | 15.72 | 15.65 | 257 | 1201 | 620 | 176 | + | + | Stable | Predominant central |
7 | 63 | 0.15 | 11.75 | 17.25 | 268 | 1190 | 346 | 185 | + | − | Stable | Predominant central |
8 | 77 | 0.09 | 16.51 | 14.85 | 254 | 1287 | 634 | 162 | + | + | Stable | Predominant central |
9 | 74 | 0.00 | 18.62 | 18.06 | 167 | 499 | 243 | 160 | + | + | Stable | Predominant central |
10 | 80 | 0.09 | 17.65 | 17.00 | 263 | 1946 | 429 | 157 | + | + | Stable | Predominant central |
11 | 76 | 0.04 | 10.25 | 15.68 | 217 | 1107 | 314 | 138 | + | − | Stable | Predominant central |
|
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|
||||||||||||
1 | 70 | 0.00 | 12.75 | 13.77 | 222 | nd | 397 | 164 | + | − | Instable | Predominant eccentric |
2 | 68 | 0.09 | 11.75 | 12.45 | 169 | nd | 653 | 186 | + | + | Stable | Predominant central |
3 | 71 | 0.52 | 8.00 | 14.00 | 249 | nd | 750 | 103 | − | − | Instable | Poorly central |
4 | 82 | 0.30 | 7.50 | 8.50 | 190 | nd | 678 | 149 | − | − | Relatively instable | Predominant central |
5 | 76 | 0.09 | 10.00 | 9.10 | 180 | nd | 542 | 175 | + | − | Stable | Predominant central |
6 | 71 | 0.52 | 3.37 | 6.25 | 261 | nd | 920 | 112 | − | − | Instable | Predominant central |
7 | 78 | 0.15 | 10.60 | 10.20 | 134 | nd | 455 | 157 | + | − | Stable | Predominant central |
LogMAR best-corrected visual acuity; mean central and total retinal sensitivity (mCRS and mTRS) in dB; LMH diameters and central foveal thickness (CFT) in microns; interdigitation zone and ellipsoid zone (IZ/EZ) and the external limiting membrane (ELM).
Functional parameters showed a significative difference in both visual acuity (
Statistical analysis of demographical characteristics and functional and morphological parameters, considered for all patients and according to tractional and degenerative LMH groups. LogMAR best-corrected visual acuity; mean central and total retinal sensitivity (mCRS and mTRS) in dB; LMH diameters and central foveal thickness (CFT) in microns.
All patients | Morphology |
| ||
---|---|---|---|---|
Tractional LMH | Degenerative LMH | |||
N | 18 | 11 | 7 | — |
Age | 72.5 (68.0; 76.0) | 73.0 (68.0; 76.0) | 71.0 (70.0; 78.0) | 0.61a |
BCVA | 0.09 (0.0; 0.15) | 0.0 (0.0; 0.09) | 0.15 (0.09; 0.52) |
|
mCRS | 13.5 (10.3; 16.5) | 16.2 (14.2; 17.7) | 10.0 (7.5; 11.8) |
|
mTRS | 15.2 (12.5; 16.3) | 15.9 (15.5; 17.0) | 10.2 (8.5; 13.8) |
|
LMH depth | 235.5 (190.0; 263.0) | 257.0 (205.0; 278.0) | 190.0 (169.0; 249.0) | 0.06a |
LMH diameter | 539.5 (397.0; 650; 0) | 429.0 (314.0; 620.0) | 653.0 (455.0; 750.0) |
|
CFT | 164.5 (157.0; 185.0) | 170.0 (160.0; 186.0) | 157.0 (112.0; 175.0) | 0.12a |
Stable fixation, |
12 (66.7%) | 9 (81.8%) | 3 (42.9%) | 0.14b |
Predominantly central fixation status, |
15 (83.3%) | 10 (90.9%) | 5 (71.4%) | 0.53b |
Median (25° percentile; 75° percentile) for continuous variables;
Considering morphological parameters, tractional and degenerative LMHs showed no significant differences in central foveal thickness: 170 (160; 186)
Table
Statistical analysis of demographical characteristics and functional and morphological parameters, considered for all patients and according to IZ/EZ-ELM alteration groups. LogMAR best-corrected visual acuity; mean central and total retinal sensitivity (mCRS and mTRS) in dB; LMH diameters and central foveal thickness (CFT) in microns. Interdigitation zone and ellipsoid zone (IZ/EZ) and the external limiting membrane (ELM).
All patients | IZ/EZ-ELM integrity |
| ||
---|---|---|---|---|
No alteration | Layers alteration | |||
N | 18 | 10 | 8 | — |
Age | 72.5 (68.0; 76.0) | 72.5 (68.0; 75.0) | 73.5 (70.5; 77.0) | 0.56a |
BCVA | 0.09 (0.0; 0.15) | 0.0 (0.0; 0.09) | 0.15 (0.07; 0.41) |
|
mCRS | 13.5 (10.3; 16.5) | 16.4 (15.7; 17.7) | 10.1 (7.8; 11.2) |
|
mTRS | 15.2 (12.5; 16.3) | 15.8 (14.9; 16.7) | 12.0 (8.8; 14.8) |
|
LMH depth | 235.5 (190.0; 263.0) | 255.5 (202.0; 278.0) | 219.5 (185.0; 255.0) | 0.36a |
LMH diameter | 539.5 (397.0; 650; 0) | 569.0 (410.0; 634.0) | 498.5 (371.5; 714.0) | 0.70a |
CFT | 164.5 (157.0; 185.0) | 173.0 (162.0; 186.0) | 153.0 (125.0; 169.5) |
|
Stable fixation, |
12 (66.7%) | 8 (80.0%) | 4 (50.0%) | 0.32b |
Predominantly central fixation status, |
15 (83.3%) | 9 (90.0%) | 6 (75.0%) | 0.56b |
Median (25° percentile; 75° percentile) for continuous variables;
In particular, visual acuity decreases in presence of IZ/EZ disruption: 0.00 (00; 0.09) LogMAR vs 0.15 (0.07; 0.41) LogMAR, respectively. Retinal sensitivity showed the same trend: both mCRS and mTRS decreased from 16.4 (15.7; 17.7) dB to 10.1 (7.8; 11.2) dB and from 15.8 (14.9; 16.7) dB to 12.0 (8.8; 14.8) dB, respectively (
Considering fixation parameters, the eyes showing integrity of both layers present a more frequent stable fixation and a predominantly central fixation status. These data, however, did not reach a statistical significance, probably due to the relatively small sample size.
Considering the morphological parameters of macular hole, the disruption of retinal layers is associated with a reduction in CFT, respectively, 173 (162; 186)
Considering the integrity of IZ/EZ and ELM in both tractional LMHs and degenerative LMHs, we found that more than 81% of tLMHs present a preservation of external layers compared to 14.2% of dLMHs (
Figure
Distribution of eyes according to IZ/EZ and ELM integrity, analyzing functional and morphological parameters. Best-corrected visual acuity (BCVA) in LogMAR; mean central and total retinal sensitivity (mCRS and mTRS) in dB; LMH depth, LMH diameter and central foveal thickness (CFT) in microns.
Nowadays, LMHs represent a defined macular pathology, classified inside the large chapter of vitreomacular pathologies secondary to an alteration to the vitreoretinal interface [
The gold standard for the diagnosis and clinical characterization of LMHs is currently OCT imaging, which provides not only qualitative but also quantitative data on this pathology.
Govetto et al. in 2016 defined tractional and degenerative subtypes of LMH by means of OCT examination [
LMH subgroups were characterized by the same origin, but with different structure and evolution, in particular due to the evidence of an epiretinal tissue proliferation [
In our study, we combined a detailed description of OCT retinal modifications in LMHs with a complete functional evaluation by means of visual acuity and microperimetry examination. Microperimetry is able to quantify foveal and perifoveal retinal sensitivity in an exact fundus-related modality, thus adding detailed information regarding the degree and pattern of macular alteration. The importance of microperimetry was recently underlined by our group into two published clinical studies, in which we investigated the correlation between morphological modifications, retinal sensibility, and fixation status in patients who underwent surgery for epiretinal macular membranes and in patients treated with an intravitreal slow-releasing steroid implant for retinal vein occlusion [
The present study underlines the morphological differences between tractional and degenerative LMH. The presence of a tractional ERM in the tLMHs increases LMH depth (median 257
Degenerative LMHs present larger LMH diameter than tLMHs probably due to progressive retinal degeneration and less tangential traction. Conversely, CFT was similar, despite a different morphology of the foveola (foveal bump in degenerative LMHs and foveolar sparing in tractional LMH).
Considering visual function, we showed a difference between tractional and degenerative LMHs, reflecting different morphological characteristics, as we showed above. Visual acuity, total and central retinal sensitivity appeared significantly higher in tractional LMHs. Considering stability and status of the fixation, tractional LMHs eyes show a prevalent central (90% of eyes) and stable (81.8% of eyes) fixation compared to degenerative LMH eyes. The ability of patients to maintain stability of fixation ensures high quality of visual function while reading or for near activities, as documented also in the case of macular pucker and macular hole, in pre- and postsurgery follow-up [
As the second step, we evaluated the integrity of the outer retinal layers, which represents a pathognomonic sign of visual acuity preservation. Several authors have described impaired visual recovery in patients affected by diabetic macular edema or exudative AMD when the IZ/EZ was damaged [
To better understand the role of ELM and IZ/EZ, we divided patients according to outer retinal layers integrity (Table
Tractional and degenerative LMHs present different morphological features due to specific ERM characteristics. Despite inner modification of the fovea due to tractional schisis or horizontal traction with foveal bump, the visual function is influenced by outer retinal layers alterations that involve the photoreceptor complex and cause qualitative and quantitative visual impairment.
Early identification of these alterations may be useful to retina experts for LMHs follow-up or to evaluate the surgical approach.
Limitation of our study was the relatively small patient population, influenced by the low prevalence of this type of pathology and its subclinical symptoms. High-resolution OCT and deep functional analysis (OCT and superimposed microperimetry) may allow us to effectively characterize patients and evaluate their clinical status. A prospective study could be helpful in order to investigate clinical progression of different LMH subtypes and to evaluate the opportunity for surgical intervention [
Our research revealed interesting elements about LMHs: tractional and degenerative LMHs show distinctive functional features that reflect their morphological differences. In particular, tractional LMHs revealed higher visual acuity and retinal sensitivity due to the relative preservation of the outer retinal layers compared to degenerative LMHs.
In order to correctly evaluate foveal degenerative pathologies with slow progression, such as LMH, a multimodal imaging is of fundamental importance. High-resolution OCT associated with microperimetry reveals the morphological and functional modifications of the retina.
The statistical data used to support the findings of this study are available from the corresponding author upon request.
The authors declare that there are no conflicts of interest regarding the publication of this paper.
The research and publication have been funded by Personal University Research Funds of the authors. Special thanks are due to Prof. Giovanni Veronesi MD, PhD, from the Research Center in Epidemiology and Preventive Medicine (EPIMED), Department of Medicine and Surgery-University of Insubria, for his valuable contribution to the statistical analysis of this study.