To evaluate the morphologic features of the photoreceptor layer (by spectral-domain optical coherence tomography) and functional parameters in patients with a lamellar macular hole.
Prospective, multicenter, observational case series.
Fifty-four patients with lamellar macular hole were enrolled in the study. All patients underwent a complete ophthalmologic examination, including best-corrected visual acuity (BCVA) testing, MP1 microperimetry, and spectral-domain optical coherence tomography. For each patient, 2 experienced masked observers evaluated the integrity of photoreceptor inner segment/outer segment (IS/OS) junction and external limiting membrane (ELM) line.
Spectral-domain optical coherence tomography analysis showed complete integrity of the IS/OS junction and ELM line in 40 eyes (group A), partial or complete disruption of the IS/OS junction with an intact ELM line in 8 eyes (group B), and an alteration of both IS/OS junction and ELM line in 6 eyes (group C). Mean BCVA, total retinal sensitivity, and fixation stability were significantly better in groups A and B than in group C (both P < .05, Tukey–Kramer test), whereas there was no significant difference between groups A and B. Mean central retinal sensitivity was significantly different among all 3 groups (all P < .05, Tukey–Kramer test). The grade of integrity of the foveal photoreceptor layer was correlated significantly with mean BCVA ( r = −0.57; P < .001), mean central retinal sensitivity ( r = 0.52; P < .001), and total retinal sensitivity ( r = 0.44; P < .001).
In lamellar macular hole, the morphologic features of the foveal photoreceptor layer consistently are correlated with BCVA and central retinal sensitivity. Preservation of the ELM is related to the maintenance of visual acuity.
The term lamellar macular hole (LMH) to describe a macular lesion resulting from cystoid macular edema was introduced by Gass in 1975. Subsequently, lamellar hole was described as an abortive process in the formation of a full-thickness macular hole; the patient has relatively preserved visual acuity, usually 20/40 or better, and a stable, round, well-circumscribed reddish macular lesion.
Optical coherence tomography (OCT) evaluation has improved the diagnosis of lamellar holes, because it allows visualization of retinal anatomic features with near microscopic resolution. With OCT investigation, LMHs are diagnosed easily, and their characteristic features of non–full-thickness defects of the macula with an irregular foveal contour and a schisis between inner and outer retinal layers, without any defect of the photoreceptor layer, have been defined as criteria for diagnosis.
The introduction of spectral-domain (SD) OCT has improved the speed and sensitivity of the examination. SD OCT scanning at a higher resolution allows visualization of the intraretinal architectural morphologic features, especially at the level of the external limiting membrane (ELM) and the photoreceptor inner segment/outer segment (IS/OS) junction, which may indicate the integrity of the photoreceptor layer. The integrity of this layer has been found to correlate with maintenance of visual function in patients with a variety of retinal diseases, including age-related macular degeneration, macular hole, central serous chorioretinopathy, and diabetic macular edema.
To characterize visual impairment, features of visual function other than the best-corrected visual acuity (BCVA) must be evaluated. It has been shown that more detailed information about a patient’s visual function can be gathered by microperimetry than by visual acuity measurement alone, and that distance visual acuity can underestimate the functional benefit of a treatment as compared with microperimetry. Microperimetry provides exact localization and quantification of retinal sensitivity in the entire macular region and automatic eye tracking for evaluating the fixation pattern.
The purpose of this study was to investigate, in eyes with LMH, the morphologic features of foveal photoreceptors, in particular the status of the ELM line and the IS/OS junction, and to assess the correlation between morphologic changes and functional deficits as measured by visual acuity assessment and microperimetry.
In this observational study, we included all consecutive patients with a diagnosis of LMH examined at the Department of Ophthalmology, University of Catania, Catania, Italy, and at the Fondazione G.B. Bietti, IRCCS, Rome, Italy, between January 2010 and May 2011. LMH were diagnosed based on SD OCT characteristics proposed by Witkin and associates. Patients were enrolled if the following characteristics were present in at least 1 of the scans: (1) an irregular foveal contour; (2) a break in the inner fovea; (3) separation of the inner from the outer foveal retinal layers, leading to an intraretinal split; (4) absence of a full-thickness foveal defect.
Exclusion criteria were the presence in the affected eye of refractive errors of more than ± 5 diopters, astigmatism of more than 2 diopters, history of amblyopia, age-related macular degeneration, diabetes mellitus, retinal vascular occlusion, vitreous hemorrhage, a history of intraocular surgery other than uncomplicated cataract surgery, significant cataract graded at more than N03 or NC3 according to the Lens Opacity Classification Scheme, and eyes with low-quality, unreliable OCT images. In cases of bilateral LMH, 1 eye was selected randomly.
All subjects received a complete ophthalmologic examination, including the measurement of BCVA, slit-lamp biomicroscopy, intraocular pressure determination, binocular indirect ophthalmoscopy, and fundus photography. BCVA was measured using Early Treatment Diabetic Retinopathy Study charts at 4 m distance by a single, independent, well-trained, experienced orthoptist in each center who was masked to the study. Vision results were quantified in logarithm of the minimal angle of resolution units. Each patient, on the same day, first underwent microperimetry and then underwent SD OCT examination.
In both centers, the MP-1 microperimeter (Nidek Technologies, Padua, Italy) was used. After the pupils were dilated (1% tropicamide), a reference frame was obtained with the integrated infrared camera. We used a 4-2 double-staircase test strategy with white background illumination set at 4 apostilbs and the starting stimulus light attenuation set at 10 dB. Then, a grid of 45 stimuli with a Goldmann III stimulus size and a time between stimuli of 1 second was projected onto the central 8 degrees. A bright red cross of 2 degrees was used for the fixation target. For assessment of fixation, the fundus movements were tracked during examination. The patient’s mean retinal sensitivity (total sensitivity) and the mean sensitivity of the central 13 points within 2 degrees (central sensitivity) was calculated. Fixation stability was calculated as the percentage of fixation points within the 2-degree diameter circle. In all patients, microperimetry was performed twice within 1 week to rule out potential learning effects, and the second test was used for the analysis. Patients underwent a brief training session at the beginning of each test. All imaging sessions were performed after 5 minutes of visual adaptation. At each center, the examinations were carried out by the same experienced ophthalmologists (M.T., Catania; A.C., Rome). Both participating centers used the same MP1 software version (version 1.4.2). To avoid bias resulting from instrument variability, all microperimeters were calibrated accurately by the same experienced technician, and the parameters of the examination were standardized at the 2 centers.
SD OCT images were obtained with the Spectralis OCT version 126.96.36.199 (Heidelberg Engineering, Heidelberg, Germany) with Heidelberg Eye Explorer version 188.8.131.52 (Heidelberg Engineering). At each center, all OCT examinations were carried out by a certified operator (M.Z., Catania; B.B., Rome) who was unaware of other information on the eyes. According to the protocol, radial 20-degree, 6-line scans centered on the fovea were obtained for each eye. More than 25 scans were averaged for each measurement. Only images with a quality score of more than 25 were selected as high-quality images. The integrity of the IS/OS and ELM was evaluated by using the photoreceptor IS/OS junction and ELM line on the gray-scale SD OCT images. Both the ELM line and the photoreceptor IS/OS junction were evaluated on each of the radial 6-line scans for 500 μm in either direction of the center of the fovea and were defined as intact when the line was continuous, disrupted when the line was interrupted by gaps shorter than 200 μm, or completely absent when the gaps were 200 μm or longer. On the basis of the appearance of 2 lines, 6 levels of integrity were described: VI, both the IS/OS junction and ELM line were intact; V, the IS/OS junction was disrupted, but the ELM line was intact; IV, the IS/OS junction was absent, but the ELM line was intact; III, both the IS/OS junction and the ELM line were disrupted; II, the IS/OS junction was absent and the ELM was disrupted; and I, both and the IS/OS junction and the ELM line were absent. According to the integrity of the foveal photoreceptor layer, the eyes were divided into 3 subgroups: group A, eyes with complete integrity of the IS/OS junction and the ELM line; group B, eyes with partial or complete disruption of the IS/OS junction with an intact ELM line; and group C, eyes with disruption of the ELM line. Two masked expert investigators at each center (M.R., A.L., Catania; M.V., M.P., Rome) interpreted the SD OCT images. When there was disagreement, a third investigator was consulted for the final decision.
All values were presented as mean ± standard deviation. Descriptive analysis was performed on the integrity of the IS/OS junction and the ELM line. The reliability of the IS/OS junction and ELM line grading was determined with weighted κ statistics and intraclass correlation coefficients (ICCs). The presence of correlation between the 6 levels of integrity of the foveal photoreceptor layer and BCVA and microperimetry parameters was tested by using the Spearman correlation coefficient. The analysis of variance was used to determine whether there were any differences in BCVA and microperimetry parameters among the 3 different subgroups (groups A, B, and C) on the basis of photoreceptor layer integrity; if significant, multiple comparisons were performed with the Tukey-Kramer test. A P value less than .05 was considered statistically significant. Statistical analysis of the data used the Statistical Packages for the Social Sciences version 17.0 for Windows (SPSS Inc, Chicago, Illinois, USA).
Sixty eyes of 60 consecutive patients with a diagnosis of LMH were evaluated; of these, 6 eyes were excluded (2 for other macular disease, 2 for refractive error more than ± 5 diopters, 1 for significant cataract, and 1 for previous vitrectomy). Therefore, 54 eyes of 54 patients met the study criteria and were enrolled. The demographic and clinical characteristics of the enrolled patients are reported in Table 1 . High-quality SD OCT scans were obtained for each patient, and none were eliminated from the study secondary to inability to grade the photoreceptor layer. The ICC between observers for the grading of the IS/OS junction was 0.96 (95% confidence interval [CI], 0.92 to 0.97), and the ICC between observers for the status of the ELM line was 0.82 (95% CI, 0.70 to 0.89). The κ coefficient for the status of the IS/OS junction was 0.91 (95% CI, 0.78 to 1.03) and that for the status of the ELM line was 0.81 (95% CI, 0.56 to 1.07).
|Study Group (n = 54)|
|Gender, n (%)|
|Eye, n (%)|
|Mean ± SD age (y)||68 ± 8|
|Mean ± SD BCVA (logMAR)||0.15 ± 0.16|
|Mean ± SD central retinal thickness (μm)||308 ± 52|
|Mean ± SD residual foveal thickness (μm)||119 ± 38|
|Epiretinal membrane, n (%)||52 (96%)|
|Vitreofoveal separation, n (%)||9 (17%)|
|Mean ± SD central retinal sensitivity (dB)||16.0 ± 3.0|
|Mean ± SD total retinal sensitivity (dB)||17.0 ± 2.3|
|Mean ± SD fixation stability (%)||90.0 ± 10.4|
At SD OCT examination, 40 eyes (74%) showed complete integrity of the IS/OS junction and ELM line, whereas 14 eyes (26%) had alterations in the photoreceptor layer: in detail, 7 eyes (13%) had a disrupted IS/OS junction with an intact ELM line, 1 (2%) had a completely absent IS/OS junction with an intact ELM line, 2 (4%) had disrupted IS/OS junction and ELM line, 4 (7%) had an absent IS/OS junction and disrupted ELM line; no eye had a completely absent ELM line. Spearman regression analysis showed that the degree of integrity of the photoreceptor layer was correlated significantly with BCVA ( r = −0.57; P < .001), total retinal sensitivity ( r = 0.44; P = .001), and central retinal sensitivity ( r = 0.52; P < .001), but not with fixation stability ( P = not significant).
Table 2 shows the subgroup analysis of groups A, B, and C according to the integrity of the photoreceptor layer. Mean BCVA, mean central retinal sensitivity, mean total retinal sensitivity, and mean fixation stability were significantly different among the 3 groups. For mean BCVA, mean total retinal sensitivity and mean fixation stability, the values for groups A and B were significantly higher than that for group C ( P < .05, Tukey–Kramer test), whereas there was no significant difference between groups A and B ( P = not significant). The mean central retinal sensitivity in groups A and B was significantly higher than that in group C ( P < .001, Tukey–Kramer test), and that in group A was significantly higher than that in group B ( P < .05, Tukey–Kramer test; Figure 1 ). Examples of OCT and microperimetry findings of the patients in the groups A, B, and C are displayed in Figure 2 .
|Photoreceptor Layer Integrity||P Value|
|Eyes with Preserved IS/OS and ELM: Group A (n = 40)||Eyes with Disrupted IS/OS and Preserved ELM: Group B (n = 8)||Eyes with Disrupted IS/OS and ELM: Group C (n = 6)||ANOVA||Tukey–Kramer|
|BCVA, logMAR||0.08 ± 0.05||0.13 ± 0.09||0.30 ± 0.11||.000||NS a|
|.000 b c|
|Total sensitivity, dB||17.7 ± 1.5||16.7 ± 2.5||13.1 ± 2.4||.000||NS a|
|Central sensitivity, dB||17.1 ± 2||15 ± 3||10.5 ± 2.4||.000||.047 a|
|Fixation stability, %||92 ± 8||91 ± 11||78 ± 16||.006||NS a|