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Retina  |   May 2014
Asymmetrical Recovery of Cone Outer Segment Tips Line and Foveal Displacement After Successful Macular Hole Surgery
Author Affiliations & Notes
  • Yuji Itoh
    Kyorin Eye Center, Kyorin University School of Medicine, Tokyo, Japan
  • Makoto Inoue
    Kyorin Eye Center, Kyorin University School of Medicine, Tokyo, Japan
  • Tosho Rii
    Kyorin Eye Center, Kyorin University School of Medicine, Tokyo, Japan
    Department of Ophthalmology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
  • Yoshimasa Ando
    Kyorin Eye Center, Kyorin University School of Medicine, Tokyo, Japan
  • Akito Hirakata
    Kyorin Eye Center, Kyorin University School of Medicine, Tokyo, Japan
Investigative Ophthalmology & Visual Science May 2014, Vol.55, 3003-3011. doi:10.1167/iovs.14-13973
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      Yuji Itoh, Makoto Inoue, Tosho Rii, Yoshimasa Ando, Akito Hirakata; Asymmetrical Recovery of Cone Outer Segment Tips Line and Foveal Displacement After Successful Macular Hole Surgery. Invest. Ophthalmol. Vis. Sci. 2014;55(5):3003-3011. doi: 10.1167/iovs.14-13973.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose.: To determine whether the photoreceptor outer segments recover symmetrically after successful macular hole surgery, and whether the recovery is correlated with the degree of foveal displacement.

Methods.: This was a retrospective, interventional case series. The medical records of 35 patients (n = 35 eyes) with a surgically closed macular hole were reviewed. Spectral-domain optical coherence tomography (SD-OCT) was used to obtain cross-sectional images across the fovea horizontally and vertically. The lengths of cone outer segment tips (COST) line defect in the temporal, nasal, superior, and inferior sectors of the fovea, the best-corrected visual acuity (BCVA), and the papillofoveal distance were measured before and at 6 and 12 months after the surgery.

Results.: The temporal COST line defect was significantly longer than the nasal length defect preoperatively (P = 0.031), at 6 months (P < 0.001), and at 12 months (P = 0.038) postoperatively. The length of the temporal COST line defect was significantly correlated with the BCVA preoperatively (P = 0.014) and at 6 months postoperatively (P = 0.001). The papillofoveal distance was significantly shorter at 6 months (P = 0.029) and 12 months (P = 0.043) postoperatively than at the baseline. The center of the COST line defect was located further temporally from the fovea postoperatively, and the distance was shorter than the nasal foveal displacement at 6 months (158.8 ± 167.0 μm, P = 0.13) and 12 months (244.8 ± 172.7 μm, P = 0.008).

Conclusions.: The restoration of the temporal COST line was delayed after successful macular hole surgery. In addition, the fovea was displaced more nasally than the center of the COST line defect which recovered centripetally. (ClinicalTrials.gov number, NCT01959776.)

Introduction
The images of the spectral-domain optical coherence tomography (SD-OCT) clearly show three highly reflective layers in the outer retina; the external limiting membrane (ELM), photoreceptor inner and outer segment (IS/OS) junction line, and the cone outer segment tips (COST) line. 1,2 The recovery of these structures in the OCT images after surgery for an epiretinal membrane, 3 macular hole, 47 diabetic macular edema, 8,9 and rhegmatogenous retinal detachment 10 was significantly correlated with the best-corrected visual acuity (BCVA). We have reported that the restoration of the COST line was the factor most highly correlated with the postoperative BCVA after successful macular hole closure. 6,7 The recovery of the COST line was found to occur centripetally, and a shorter COST line defect in the macular area was significantly correlated with a better BCVA. 
The success rate of macular hole surgery after vitrectomy with internal limiting membrane (ILM) peeling and gas tamponade is higher than that after vitrectomy without ILM peeling and gas tamponade. 1113 In addition, the successful anatomical closure of a macular hole leads to significantly better visual acuities. Thus, ILM peeling and gas tamponade during vitrectomy have become standard procedures to treat macular holes with the use of adjuvants to make the ILM more visible. 1416 However, it has been reported that ILM peeling can cause an increase in the dissociated optic nerve fiber layer appearance, 17,18 thinning of the macula, 19 swelling of the arcuate retinal nerve fiber layer, 20 dimpling of the inner retina, 21 reduction of the thickness of the ganglion cell complex, 22 defects of the inner retina, 23 microscotomas, 24 and decreased retinal sensitivity. 24  
A displacement of the fovea toward the optic disc after vitrectomy with ILM peeling for diabetic macular edema 25 and macular hole was recently reported. 26,27 Kawano and colleagues 26 suggested that the distance between the optic disc and the center of the macular hole was significantly shorter after successful closure of a macular hole. However, Yoshikawa and colleagues 25 stated that the shortening in eyes with diabetic macular edema developed only in the inner retina and not the outer retina because previously treated laser scars did not move. There was also an asymmetry of the parafoveal retinal thickness so that the temporal retina was thinner and the nasal retina thicker at the site of the displaced fovea and the tissues involved in the displacement after surgery. 19,28 However, it has not been determined whether the recovery of the microstructures of the photoreceptors is asymmetrical after successful macular hole closure by vitrectomy. 
Thus, the purpose of this study was to determine whether the COST line, IS/OS line, and ELM line around the fovea recovered symmetrically, and whether the asymmetrical recovery of the COST line was significantly correlated with the foveal displacement and postoperative BCVA in eyes after vitrectomy with ILM peeling. 
Patients and Methods
Of the 193 eyes of 185 patients that underwent macular hole surgery between July 2009 and March 2012 at the Kyorin Eye Center, eyes with any macular disease other than macular hole, other retinal diseases, glaucoma, other optic nerve diseases, and high myopia (refractive errors greater than −8.0 diopters or axial length more than 26.0 mm) were excluded. Only the medical records of consecutive patients with a surgically closed idiopathic macular hole and follow-up times of at least 6 months were reviewed. All patients were diagnosed with either a stage 2, 3, or 4 idiopathic macular hole according to Gass' classification. The preoperative data collected included the age, sex, right or left eye, stage of macular hole, Snellen BCVA, length of the ELM line, IS/OS line, and COST line defect, the distance from the optic disc margin to the fovea or center of macular hole, and cross-sectional retinal area from the disc margin to the edge of macular hole or the disc margin to the fovea. The BCVA was measured by the same examiner in the same room under similar illumination. The decimal BCVA was converted to logMAR units for the statistical analyses. 
All of the patients had a comprehensive ophthalmologic examination before and 6 and 12 months after the surgery. The examinations included fundus examinations by binocular indirect ophthalmoscopy and noncontact lens slit-lamp biomicroscopy, fundus photography, and fundus autofluorescence imaging by confocal scanning ophthalmoscopy (Heidelberg Retina Angiograph 2; Heidelberg Engineering, Heidelberg, Germany). Cross-sectional images of the macular area were obtained by SD-OCT (Spectralis; Heidelberg Engineering). These examinations were performed on the same day in all patients. 
All surgeries were performed after the patients received a detailed explanation of the surgical and SD-OCT procedures. An informed consent was obtained from all patients, and the procedures used adhered to the tenets of the Declaration of Helsinki. The study protocol was approved by the Institutional Review Committee of the Kyorin University School of Medicine, and all of the patients consented to our review of their medical records. This clinical study has been registered at the United States National Institutes of Health (www.clinicaltrials.gov) as “Asymmetrical Recovery of Cone Outer Segment Tips and Foveal Displacement After Macular Hole Surgery” with a reference number of NCT01959776. The main outcome measures were the length of cone outer segment tips line defect from the fovea and papillofoveal distance in the SD-OCT images. 
The surgery was performed by one of the three retina specialists (YI, MI, AH). A standard three-port pars plana vitrectomy (PPV) was used to close the macular hole under 2% lidocaine retrobulbar anesthesia. An intravitreal injection of triamcinolone acetonide (MaQaid; Wakamoto Pharmaceutical Co., Ltd., Tokyo, Japan or Kenacort-A; Bristol Pharmaceuticals KK, Tokyo, Japan) was used to make the vitreous gel and ILM more visible. Core vitrectomy was performed with the creation of a posterior vitreous detachment if it was not present, and the ILM was removed in all cases. Internal limiting membrane was peeled in an area of 1 to 2 disc diameters around the macular hole symmetrically. The lens was extracted from all patients aged >55 years; and all cataractous lenses were removed by phacoemulsification with an implantation of an intraocular lens. Room air or nonexpansive 20% sulfur hexafluoride (SF6) was used to tamponade the retina, and the patients were instructed to maintain a facedown position for 3 to 4 days after the surgery. Anatomical success was defined as the presence of a flat and closed macular hole postoperatively as confirmed by slit-lamp biomicroscopy, SD-OCT, and the absence of autofluorescence at the site of the macular hole. 
The macular area was scanned with the SD-OCT instruments with at least 70 repeated scans, and high quality 9-mm scan images were obtained. The lengths of the ELM line defect, IS/OS line defect, and COST line defect across the fovea in the horizontal and vertical scans were measured on the SD-OCT images using software embedded in the instrument. The center of the macular hole was determined to be the anatomical center of the dehiscent macular hole preoperatively. The foveal center or the center of the closed macular hole was defined as the hyperreflective junction of the closed macular hole or the center of foveal depression in the SD-OCT images. The inner retinal layers from the nerve fiber layer to Henle's layer were observed in the periphery and, when traced to the fovea, these layers disappeared as reported. 25 The center point of this area was considered to be the foveal center. 
The length of the ELM line, IS/OS line, and COST line defects in the temporal, nasal, superior, and inferior sectors—i.e., the Early Treatment Diabetic Retinopathy Study sectors—were also measured in the SD-OCT vertical and horizontal images. Preoperatively, the length of the ELM line defect, IS/OS line defect, and the COST line defects were measured from the center of the macular hole. 
The papillofoveal distance was measured manually as the distance between the center of the macular hole or the fovea and the optic disc margin in the SD-OCT images of the horizontal section across the fovea using software embedded in the instrument (Fig. 1). To determine the papillofoveal cross-sectional area between the fovea and the optic disc margin, the SD-OCT images of 9-mm width were uploaded to a computer, and the total number of pixels of the sensory retinal area between the optic disc margin and the center of macular hole or the fovea was counted with the ImageJ software (http://imagej.nih.gov/ij/; provided in the public domain by the National Institutes of Health, Bethesda, MD, USA). The areas of fluid including intraretinal cyst or subretinal fluid were subtracted to evaluate only the cellular components of the papillofoveal cross sections (Fig. 2). Two experienced investigators (YI, TR), who were masked to the patients' information including the postoperative period and the BCVA, measured the length of COST line, IS/OS line, and ELM line defects and papillofoveal distance on each SD-OCT image independently. 
Figure 1
 
Horizontal cross-sectional SD-OCT images. (A) The papillofoveal distance from the center of the macular hole at the baseline is longer than that at 6 months after surgery (B).
Figure 1
 
Horizontal cross-sectional SD-OCT images. (A) The papillofoveal distance from the center of the macular hole at the baseline is longer than that at 6 months after surgery (B).
Figure 2
 
Papillofoveal cross-sectional retinal area from the optic disc to the macular hole. (A) The total pixels of the papillofoveal area (within yellow line) are measured before vitrectomy and 6 months after vitrectomy (B). The areas of intraretinal cysts (within blue line) are subtracted from the total area.
Figure 2
 
Papillofoveal cross-sectional retinal area from the optic disc to the macular hole. (A) The total pixels of the papillofoveal area (within yellow line) are measured before vitrectomy and 6 months after vitrectomy (B). The areas of intraretinal cysts (within blue line) are subtracted from the total area.
The Mann-Whitney U tests were used to compare two groups. For multiple comparisons, the three sets of data were analyzed using one-way ANOVA and Kruskal-Wallis tests. Multivariate analyses were also performed to determine which sector of COST line defect was correlated with the BCVA preoperatively, and at 6 and 12 months after surgery. 
Results
One eye with age-related macular degeneration, one eye with Coats diseases, five eyes with glaucoma, and three eyes with high myopia were excluded. In addition, six eyes were also excluded because of a history of trauma, 14 eyes with earlier vitreoretinal surgeries, seven eyes in which the macular hole was not closed, and four eyes with an epiretinal membrane were also excluded. In the end, 35 eyes of 35 patients (14 men, 21 women) with refractive errors ranging from −4.75 to +2.0 diopters met the study criteria for the data analyses. 
The preoperative baseline characteristics of the 35 eyes are summarized in Table 1. The mean age was 66.2 ± 8.2 years with a range of 42 to 84 years. The preoperative stage of the macular hole was stage 2 in six eyes (17%), stage 3 in 24 eyes (69%), and stage 4 in five eyes (14%). Thirty eyes were phakic and five eyes were pseudophakic before the surgery. Combined cataract surgery was performed on 29 eyes and as a result, one eye (42-year-old man) was phakic and other 34 eyes were pseudophakic after the surgery. No eye had a severe progression of the cataract or posterior capsular opacification that could have affected the BCVA during the observational period. The mean preoperative BCVA was 0.54 logMAR units (decimal BCVA, 0.35; Snellen equivalent, 20/60). The mean BCVA after surgery was 0.18 logMAR units (decimal BCVA, 0.71; Snellen equivalent, 20/30) at 6 months; 0.16 logMAR units (decimal BCVA, 0.78; Snellen equivalent, 20/25) at 12 months. 
Table 1
 
Patient Baseline Characteristics
Table 1
 
Patient Baseline Characteristics
Numbers of eyes (patients) 35 (35)
Age, y, mean ± SD (range) 66.2 ± 8.2 (42–84)
Sex, n (%)
 Men 14 (40)
 Women 21 (60)
Eye, n (%)
 Right 17 (49)
 Left 18 (51)
Preoperative stage, n (%)
 Stage 2 6 (17)
 Stage 3 24 (69)
 Stage 4 5 (14)
Intravitreal gas tamponade during PPV, n (%)
 Air 9 (26)
 SF6 26 (74)
Combination of cataract surgery, n (%) 29 (83)
Comparison of Length of Foveal Microstructural Line Defects From Center of Macular Hole
The preoperative mean (± standard deviation) temporal length of the COST line defect (center of macular hole to margin of temporal sector) was 1093.1 ± 361.7 μm, which was significantly longer than the nasal length (940.9 ± 248.0 μm, P = 0.031, Mann-Whitney U test; Figs. 3, 4). Postoperatively, the mean temporal length of the COST line defect was significantly longer than the nasal length at 6 months (P < 0.001) and at 12 months (P = 0.038). The preoperative mean superior length of the COST line defect was 928.4 ± 192.3 μm which was not significantly longer than the length inferiorly (871.3 ± 263.0 μm, P = 0.35). The difference was also not significant at 6 months (P = 0.74) and 12 months (P = 0.80) postoperatively. 
Figure 3
 
Cone outer segment tips line defect in the horizontal and vertical sections in the SD-OCT images. A representative case in which vitrectomy was performed with ILM peeling for a macular hole. Spectral-domain OCT images across the center of the macular hole show preoperative COST line defect in the horizontal (A) and vertical (B) sections. After successful macular hole closure, the COST line defect is restored centripetally at 6 months in horizontal (C) and vertical sections (D) and at 12 months in horizontal (E) and vertical sections (F). The COST line defect is symmetrical in the vertical sections but not in the horizontal sections.
Figure 3
 
Cone outer segment tips line defect in the horizontal and vertical sections in the SD-OCT images. A representative case in which vitrectomy was performed with ILM peeling for a macular hole. Spectral-domain OCT images across the center of the macular hole show preoperative COST line defect in the horizontal (A) and vertical (B) sections. After successful macular hole closure, the COST line defect is restored centripetally at 6 months in horizontal (C) and vertical sections (D) and at 12 months in horizontal (E) and vertical sections (F). The COST line defect is symmetrical in the vertical sections but not in the horizontal sections.
Figure 4
 
Length of preoperative and postoperative COST line, photoreceptor IS/OS line, ELM line defects in horizontal and vertical sections. (A) Cone outer segment tips line defect from the center of the macular hole in the temporal sector is significantly longer than that in the nasal sector in the horizontal scan preoperatively and at 6 and 12 months after the surgery. (B) Cone outer segment tips line defect in the superior and the inferior sectors of the vertical scan are not significantly different. (C) The horizontal differences in the IS/OS line defect between the temporal and nasal sectors and (D) the vertical differences between the superior and inferior sectors, (E) the horizontal differences, and (F) the vertical differences in ELM line defect and are not significant. Preop, preoperative; NS, not significant.
Figure 4
 
Length of preoperative and postoperative COST line, photoreceptor IS/OS line, ELM line defects in horizontal and vertical sections. (A) Cone outer segment tips line defect from the center of the macular hole in the temporal sector is significantly longer than that in the nasal sector in the horizontal scan preoperatively and at 6 and 12 months after the surgery. (B) Cone outer segment tips line defect in the superior and the inferior sectors of the vertical scan are not significantly different. (C) The horizontal differences in the IS/OS line defect between the temporal and nasal sectors and (D) the vertical differences between the superior and inferior sectors, (E) the horizontal differences, and (F) the vertical differences in ELM line defect and are not significant. Preop, preoperative; NS, not significant.
The postoperative temporal and nasal lengths of the COST line defect were significantly shorter at 6 months (temporal, 718.0 ± 433.6 μm, P < 0.01; nasal, 332.1 ± 302.9 μm, P < 0.01, Kruskal-Wallis test) and at 12 months (temporal, 424.7 ± 371.0 μm, P < 0.01; nasal, 213.9 ± 241.3 μm, P < 0.01) than at the baseline. The postoperative superior and inferior lengths of the COST line defect were also significantly shorter at 6 months (403.7 ± 278.5 μm, P < 0.01; 381.4 ± 270.8 μm, P < 0.01, respectively) and at 12 months (208.3 ± 199.2 μm, P < 0.01; 226.9 ± 213.8 μm, P < 0.01, respectively) than at the baseline. The postoperative mean length of the COST line defect became progressively shorter, and the COST line recovery began at the periphery and progressed toward the center of the closed macular hole. 
The temporal and nasal lengths of the IS/OS line defect were not significantly different preoperatively (P = 0.91, Mann-Whitney U test, Fig. 4) and at 6 months (P = 0.81) and 12 months (P = 0.94) postoperatively. The superior and inferior lengths of the IS/OS line defect were not significantly different preoperatively (P = 0.82) and at 6 months (P = 0.94) and 12 months (P = 0.65) postoperatively. 
The postoperative temporal and nasal lengths of the IS/OS line defect were significantly shorter at 6 months (59.3 ± 102.2 μm, P < 0.01; 69.0 ± 153.1 μm, P < 0.01, Kruskal-Wallis test, respectively) and at 12 months (48.3 ± 77.6 μm, P < 0.01; 45.7 ± 70.3 μm, P < 0.01, respectively) than that at the baseline. The postoperative superior and inferior lengths of the IS/OS line defect were also significantly shorter at postoperative month 6 (57.6 ± 61.4 μm, P < 0.01; 146.3 ± 440.1 μm, P < 0.01, respectively) and 12 months (67.9 ± 87.4 μm, P < 0.01; 90.0 ± 135.1 μm, P < 0.01, respectively) than at the baseline. 
The temporal and nasal lengths of the ELM line defect were not significantly different preoperatively (P = 0.71, Mann-Whitney U test, Fig. 4) and also at 6 months (P = 0.61) and at 12 months (P = 0.99) postoperatively. The superior and inferior lengths of the ELM line defect were not significantly different preoperatively (P = 0.99) and also at 6 months (P = 0.40) and 12 months (P = 0.99) postoperatively. 
The postoperative temporal and nasal lengths of the ELM line defect were significantly shorter at 6 months (11.6 ± 54.4 μm, P < 0.01; 26.6 ± 124.8 μm, P < 0.01, Kruskal-Wallis test, respectively) and at 12 months (2.5 ± 8.6 μm, P < 0.01; 2.5 ± 8.4 μm, P < 0.01, respectively) than at the baseline. The postoperative superior and inferior lengths of the ELM line defect were also significantly shorter at 6 months (15.7 ± 73.7 μm, P < 0.01; 119.3 ± 559.5 μm, P < 0.01, respectively) and at 12 months (2.5 ± 8.3 μm, P < 0.01; 2.5 ± 8.4 μm, P < 0.01, respectively) than at the baseline. 
Papillofoveal Distance and Papillofoveal Area After Macular Hole Closure
The postoperative papillofoveal distances at 6 and 12 months (3763.3 ± 319.2 μm, 3723.9 ± 351.9 μm, respectively) were significantly shorter than that before the vitrectomy (3926.5 ± 302.4 μm, P = 0.029; P = 0.043, Kruskal-Wallis test, respectively, Fig. 5). The fovea was displaced nasally by 163.2 μm at 6 months and 202.6 μm at 12 months. Foveal nasal displacements greater than 50 μm occurred in 29 (83%) of the 35 eyes at postoperative month 6 and 11 (92%) of 12 eyes at 12 months. 
Figure 5
 
Papillofoveal distances before and after surgery. The papillofoveal distances at 6 and 12 months after surgery are significantly shorter than that at the baseline. The distance between the center of the COST line defect and the optic disc margin is not significant from that at the baseline. Papillofovea, papillofoveal distance; papillo-COST, distance between the center of the COST line defect and the optic disc margin. *P < 0.05.
Figure 5
 
Papillofoveal distances before and after surgery. The papillofoveal distances at 6 and 12 months after surgery are significantly shorter than that at the baseline. The distance between the center of the COST line defect and the optic disc margin is not significant from that at the baseline. Papillofovea, papillofoveal distance; papillo-COST, distance between the center of the COST line defect and the optic disc margin. *P < 0.05.
In contrast, the preoperative papillofoveal area which was 24,272.6 ± 2756.4 pixels was not significantly different from that at 6 months (24,266.5 ± 2662.0 pixels, P = 0.77, Kruskal-Wallis test) and 12 months (23,660.2 ± 2506.2 pixels, P = 0.43) postoperatively. 
Correlation Between Asymmetrical Recovery of COST Line Defect and Foveal Displacement
The center of the macular hole was displaced toward the optic disc, and the asymmetrical recovery of COST line defect that the temporal length of the COST line defect was longer than the nasal length may be due to the displacement of the fovea toward the optic disc. Thus, the distance from the center of the macular hole to the center of COST line defect was evaluated. The center of COST line defect was located on the temporal side of the center of the macular hole at 6 and 12 months after the surgery (Fig. 5). The horizontal distance from the center of the macular hole to the center of COST line defect at postoperative month 6 was 187.4 ± 153.8 μm, which was significantly longer than that at the baseline (76.1 ± 96.2 μm, P = 0.024, Mann-Whitney U test, Fig. 6). The distance at postoperative month 12 was 105.4 ± 146.7 μm, which was significantly shorter than that at postoperative month 6, but was not significantly shorter than that at the baseline (P = 0.047, P = 0.74, respectively). The center of the COST line defect was located further temporally from the fovea than that at the baseline by 107.9 ± 178.8 μm at 6 months and by 51.9 ± 154.4 μm at 12 months (Fig. 6). The displacement of the center of the COST line defect from the fovea was shorter than the foveal displacement in the nasal direction at 6 months by 158.8 ± 167.0 μm (n = 29, P = 0.13) and also at 12 months by 244.8 ± 172.7 μm (n = 12, P = 0.008). These changes indicate that the recovery of the COST line in the temporal sector was greater between 6 and 12 months than the foveal displacement. 
Figure 6
 
The distance from the center of the COST line defect to the fovea and the foveal displacement after surgery. The distance from the center of the COST line defect to the fovea increases significantly from the baseline at 6 months but not at 12 months. The distance significantly decreases at 12 months from that at 6 months. COST-fovea, distance from the center of the COST line defect to fovea. *P < 0.05.
Figure 6
 
The distance from the center of the COST line defect to the fovea and the foveal displacement after surgery. The distance from the center of the COST line defect to the fovea increases significantly from the baseline at 6 months but not at 12 months. The distance significantly decreases at 12 months from that at 6 months. COST-fovea, distance from the center of the COST line defect to fovea. *P < 0.05.
Correlation Between Asymmetrical Recovery of COST Line Defect and Visual Recovery
Forward stepwise regression analyses were performed to determine which sectors of the COST line defect were significantly correlated with the BCVA. The temporal length of the COST line defect was the factor most significantly associated with the BCVA before surgery and also at 6 months postoperatively (P = 0.014, P = 0.001, respectively; Table 2). The nasal length of the COST line defect before surgery was also significantly correlated with the BCVA before surgery (P = 0.022), but not at postoperative month 6 (P = 0.072). The superior and inferior lengths of the COST line defects were not significantly correlated with the BCVA at any observational time. At postoperative month 12, there was no significant correlation between the BCVA and the length of COST line defect in all sectors. 
Table 2
 
Foveal Microstructure and BCVA
Table 2
 
Foveal Microstructure and BCVA
Before Surgery, n = 35 6 Mo, n = 35 12 Mo, n = 19
SPRC F Value P Value SPRC F Value P Value SPRC F Value P Value
COST line defect
 Temporal 0.46 7 0.014 0.56 13 0.001 −0.30 0.64 0.46
 Nasal 0.42 5.9 0.022 0.33 3.5 0.072 0.19 0.23 0.65
 Superior −0.16 0.71 0.41 −0.033 0.031 0.86 −0.30 0.64 0.45
 Inferior 0.11 0.33 0.57 −0.12 0.39 0.54 0.37 1.02 0.35
IS/OS line defect
 Temporal −0.038 0.04 0.84 0.16 0.43 0.52 −0.48 1.79 0.23
 Nasal −0.048 0.07 0.80 −0.12 0.27 0.61 0.52 2.22 0.19
 Superior −0.16 0.75 0.40 −0.20 0.68 0.42 −0.35 0.86 0.39
 Inferior 0.27 2.3 0.14 0.20 0.72 0.41 0.30 0.58 0.47
Discussion
There is evidence that vitrectomy with ILM peeling for a macular hole is associated with changes in the thickness of the macular area. 19,22,28 Thus, Kumagai and associates 19 reported that the inner temporal retina became significantly thinner, whereas the inner nasal sector thickness did not change significantly after ILM peeling. They suggested that the differences in the thickness of the retinal nerve fiber layer (RNFL) may have led to these differential responses. They concluded that a thinner RNFL may be more affected by macular hole surgery with ILM peeling, leading to the alterations of the underlying retinal layers. 19  
There are several studies that investigated the relationships between the RNFL thickness and photoreceptor changes in eyes with different retinal diseases. Choi and associates 29 reported that a significant relationship existed between the thinning of the RNFL layer and disturbances of the photoreceptor layer in patients with optic disc drüsen. They concluded that changes in the cone photoreceptors occurred in conjunction with the expected changes of the inner retina. Pasadhika and associates also suggested that the inner retinal structures can be affected by outer retinal diseases—e.g., cone-rod dystrophy. 30  
Treumer and associates also reported that the median foveal shape was distorted after ILM peeling in epiretinal membrane surgery. 31 The fovea and the nasal parafovea remained thickened between the outer nuclear layer and the ganglion cell layer, whereas the superior, temporal, and inferior macular thickness returned to normal thickness long after the surgery. They hypothesized that the nasal side of the fovea was more vulnerable to traction and shear stress exerted by epiretinal membrane and recovered more slowly and to a lesser degree long after the surgery. 31 However, foveal displacements have been reported in patients with diabetic macular edema 25 and macular hole 26,27 after vitrectomy with ILM peeling. Yoshikawa and associates suggested that ILM peeling caused a significant shortening of the papillofoveal distance without displacement of the outer retina, which they explained was due to less elasticity of the retina. 25 The papillofoveal distance after surgery and the retinal thickness in the temporal retina were significantly correlated, and the foveal displacement toward the optic disc led to a stretching and thinning of the retinal parenchyma in the temporal subfield. 25 A stretching of the foveal tissue that resulted in significantly longer postoperative horizontal than vertical distances between the edge of the outer plexiform layer has been described after macular hole surgery. 32 This asymmetrical elongation was associated with metamorphopsia. 32  
The distance between the edge of optic disc and the fovea was significantly shorter at postoperative months 6 and 12 than that at the baseline. But the papillofoveal cross sectional area was not significantly changed at 6 and 12 months after surgery than at the baseline. We suggest that this lack of change in the papillofoveal area and shortening of the papillofoveal distance is related to the foveal displacement without any loss of cellular component of the sensory retina after the macular hole surgery with ILM peeling. 
It has been reported that the capillaries around the fovea are displaced toward the optic disc after vitrectomy with ILM peeling for diabetic macular edema. 25 However, the major vessels and photocoagulation scars are fixed indicating that there should be no displacement of the outer retina after ILM peeling. 25 In our study, the length of the COST line defect was vertically symmetrical but horizontally asymmetrical and the COST line defect in the temporal sector was longer than that in the nasal sector even after the foveal displacement toward the optic disc was considered (Fig. 7). The center of COST line defect was located temporally before and after surgery. The distance between fovea and the center of the COST line defect became longer at postoperative month 6 than at the baseline. However, the distance at postoperative month 12 became shorter than at 6 months. The displacement of the center of the COST line defect between postoperative months 6 and 12 was significantly shorter than the foveal nasal displacement during this period. These changes suggested that the delayed recovery of the COST line in the temporal sector was involved in the foveal migration displaced nasally between 6 and 12 months after macular hole surgery. We suggest that the horizontal stretching of the temporal inner retina may delay the restoration of temporal COST line compared with the nasal sector. However, we did not evaluate the retinal sensitivity around the macula. 
Figure 7
 
The illustration of foveal displacement and the center of the COST line defect. The COST line (yellow line) defect recovers centripetally after surgery and the fovea (red line) is displaced nasally toward the edge of the optic disc (blue line) at postoperative months 6 and 12. The distance between the center (yellow arrowheads) of the COST line defect and the fovea at 6 months is longer than that at baseline and the distance at 12 months is shorter than that at 6 months.
Figure 7
 
The illustration of foveal displacement and the center of the COST line defect. The COST line (yellow line) defect recovers centripetally after surgery and the fovea (red line) is displaced nasally toward the edge of the optic disc (blue line) at postoperative months 6 and 12. The distance between the center (yellow arrowheads) of the COST line defect and the fovea at 6 months is longer than that at baseline and the distance at 12 months is shorter than that at 6 months.
In addition to the postoperative asymmetrical recovery, the preoperative COST line defect was also horizontally asymmetrical. A perifoveal separation of the posterior vitreous cortex creates an anterior-posterior traction toward the fovea resulting in a dehiscence of the Müller cell cones and a full thickness macular hole. 33 Thus, the anterior-posterior vitreous traction at the temporal margin of the optic disc may be stronger, which will damage the outer retina more severely to cause a longer COST line defect in the temporal sector because the posterior vitreous cortex is attached at the optic disc when the fovea was under tension. The contractile force of the ILM with cellular proliferation above the ILM may have more effect on the temporal sector, but no studies have examined this phenomenon. 
This study has several limitations. This was a retrospective study and the number of patients studied was small. In addition, there was no control group and the follow-up period may have been too short because the average course of anatomical and functional recovery after macular surgery is considerably longer than a year. 34 The resolution of the SD-OCT used was limited and detailed images of retinal outer layer, especially the COST line, were not always obtained. Therefore, further studies with a longer follow-up period, with a larger sample size and a higher resolution SD-OCT are needed to confirm these results. In addition, we did not evaluate the papillofoveal volume of the sensory retina but the shortening of the papillofoveal distance without a change in the papillofoveal area which is an indirect evaluation of the foveal displacement. 
In conclusion, our quantitative measurements of the photoreceptor COST line defects showed that the recovery of photoreceptor COST line was vertically symmetrical but horizontally asymmetrical. In addition, the recovery of the temporal COST line was delayed compared to the nasal COST line. The fovea was displaced more nasally after surgery than the deviated COST line suggesting that the stretching force of the temporal retinal area after ILM peeling might delay the restoration of the temporal COST line defect compared to the nasal area resulting in the asymmetrical recovery of cone photoreceptor outer segments. 
Acknowledgments
The authors alone are responsible for the content and writing of the paper. 
Disclosure: Y. Itoh, None; M. Inoue, None; T. Rii, None; Y. Ando, None; A. Hirakata, None 
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Figure 1
 
Horizontal cross-sectional SD-OCT images. (A) The papillofoveal distance from the center of the macular hole at the baseline is longer than that at 6 months after surgery (B).
Figure 1
 
Horizontal cross-sectional SD-OCT images. (A) The papillofoveal distance from the center of the macular hole at the baseline is longer than that at 6 months after surgery (B).
Figure 2
 
Papillofoveal cross-sectional retinal area from the optic disc to the macular hole. (A) The total pixels of the papillofoveal area (within yellow line) are measured before vitrectomy and 6 months after vitrectomy (B). The areas of intraretinal cysts (within blue line) are subtracted from the total area.
Figure 2
 
Papillofoveal cross-sectional retinal area from the optic disc to the macular hole. (A) The total pixels of the papillofoveal area (within yellow line) are measured before vitrectomy and 6 months after vitrectomy (B). The areas of intraretinal cysts (within blue line) are subtracted from the total area.
Figure 3
 
Cone outer segment tips line defect in the horizontal and vertical sections in the SD-OCT images. A representative case in which vitrectomy was performed with ILM peeling for a macular hole. Spectral-domain OCT images across the center of the macular hole show preoperative COST line defect in the horizontal (A) and vertical (B) sections. After successful macular hole closure, the COST line defect is restored centripetally at 6 months in horizontal (C) and vertical sections (D) and at 12 months in horizontal (E) and vertical sections (F). The COST line defect is symmetrical in the vertical sections but not in the horizontal sections.
Figure 3
 
Cone outer segment tips line defect in the horizontal and vertical sections in the SD-OCT images. A representative case in which vitrectomy was performed with ILM peeling for a macular hole. Spectral-domain OCT images across the center of the macular hole show preoperative COST line defect in the horizontal (A) and vertical (B) sections. After successful macular hole closure, the COST line defect is restored centripetally at 6 months in horizontal (C) and vertical sections (D) and at 12 months in horizontal (E) and vertical sections (F). The COST line defect is symmetrical in the vertical sections but not in the horizontal sections.
Figure 4
 
Length of preoperative and postoperative COST line, photoreceptor IS/OS line, ELM line defects in horizontal and vertical sections. (A) Cone outer segment tips line defect from the center of the macular hole in the temporal sector is significantly longer than that in the nasal sector in the horizontal scan preoperatively and at 6 and 12 months after the surgery. (B) Cone outer segment tips line defect in the superior and the inferior sectors of the vertical scan are not significantly different. (C) The horizontal differences in the IS/OS line defect between the temporal and nasal sectors and (D) the vertical differences between the superior and inferior sectors, (E) the horizontal differences, and (F) the vertical differences in ELM line defect and are not significant. Preop, preoperative; NS, not significant.
Figure 4
 
Length of preoperative and postoperative COST line, photoreceptor IS/OS line, ELM line defects in horizontal and vertical sections. (A) Cone outer segment tips line defect from the center of the macular hole in the temporal sector is significantly longer than that in the nasal sector in the horizontal scan preoperatively and at 6 and 12 months after the surgery. (B) Cone outer segment tips line defect in the superior and the inferior sectors of the vertical scan are not significantly different. (C) The horizontal differences in the IS/OS line defect between the temporal and nasal sectors and (D) the vertical differences between the superior and inferior sectors, (E) the horizontal differences, and (F) the vertical differences in ELM line defect and are not significant. Preop, preoperative; NS, not significant.
Figure 5
 
Papillofoveal distances before and after surgery. The papillofoveal distances at 6 and 12 months after surgery are significantly shorter than that at the baseline. The distance between the center of the COST line defect and the optic disc margin is not significant from that at the baseline. Papillofovea, papillofoveal distance; papillo-COST, distance between the center of the COST line defect and the optic disc margin. *P < 0.05.
Figure 5
 
Papillofoveal distances before and after surgery. The papillofoveal distances at 6 and 12 months after surgery are significantly shorter than that at the baseline. The distance between the center of the COST line defect and the optic disc margin is not significant from that at the baseline. Papillofovea, papillofoveal distance; papillo-COST, distance between the center of the COST line defect and the optic disc margin. *P < 0.05.
Figure 6
 
The distance from the center of the COST line defect to the fovea and the foveal displacement after surgery. The distance from the center of the COST line defect to the fovea increases significantly from the baseline at 6 months but not at 12 months. The distance significantly decreases at 12 months from that at 6 months. COST-fovea, distance from the center of the COST line defect to fovea. *P < 0.05.
Figure 6
 
The distance from the center of the COST line defect to the fovea and the foveal displacement after surgery. The distance from the center of the COST line defect to the fovea increases significantly from the baseline at 6 months but not at 12 months. The distance significantly decreases at 12 months from that at 6 months. COST-fovea, distance from the center of the COST line defect to fovea. *P < 0.05.
Figure 7
 
The illustration of foveal displacement and the center of the COST line defect. The COST line (yellow line) defect recovers centripetally after surgery and the fovea (red line) is displaced nasally toward the edge of the optic disc (blue line) at postoperative months 6 and 12. The distance between the center (yellow arrowheads) of the COST line defect and the fovea at 6 months is longer than that at baseline and the distance at 12 months is shorter than that at 6 months.
Figure 7
 
The illustration of foveal displacement and the center of the COST line defect. The COST line (yellow line) defect recovers centripetally after surgery and the fovea (red line) is displaced nasally toward the edge of the optic disc (blue line) at postoperative months 6 and 12. The distance between the center (yellow arrowheads) of the COST line defect and the fovea at 6 months is longer than that at baseline and the distance at 12 months is shorter than that at 6 months.
Table 1
 
Patient Baseline Characteristics
Table 1
 
Patient Baseline Characteristics
Numbers of eyes (patients) 35 (35)
Age, y, mean ± SD (range) 66.2 ± 8.2 (42–84)
Sex, n (%)
 Men 14 (40)
 Women 21 (60)
Eye, n (%)
 Right 17 (49)
 Left 18 (51)
Preoperative stage, n (%)
 Stage 2 6 (17)
 Stage 3 24 (69)
 Stage 4 5 (14)
Intravitreal gas tamponade during PPV, n (%)
 Air 9 (26)
 SF6 26 (74)
Combination of cataract surgery, n (%) 29 (83)
Table 2
 
Foveal Microstructure and BCVA
Table 2
 
Foveal Microstructure and BCVA
Before Surgery, n = 35 6 Mo, n = 35 12 Mo, n = 19
SPRC F Value P Value SPRC F Value P Value SPRC F Value P Value
COST line defect
 Temporal 0.46 7 0.014 0.56 13 0.001 −0.30 0.64 0.46
 Nasal 0.42 5.9 0.022 0.33 3.5 0.072 0.19 0.23 0.65
 Superior −0.16 0.71 0.41 −0.033 0.031 0.86 −0.30 0.64 0.45
 Inferior 0.11 0.33 0.57 −0.12 0.39 0.54 0.37 1.02 0.35
IS/OS line defect
 Temporal −0.038 0.04 0.84 0.16 0.43 0.52 −0.48 1.79 0.23
 Nasal −0.048 0.07 0.80 −0.12 0.27 0.61 0.52 2.22 0.19
 Superior −0.16 0.75 0.40 −0.20 0.68 0.42 −0.35 0.86 0.39
 Inferior 0.27 2.3 0.14 0.20 0.72 0.41 0.30 0.58 0.47
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