Current Eye Research

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Interdigitation Zone Band Restoration After Treatment of Diabetic Macular Edema Satoshi Serizawa, Kishiko Ohkoshi, Yuko Minowa & Kumiko Soejima To cite this article: Satoshi Serizawa, Kishiko Ohkoshi, Yuko Minowa & Kumiko Soejima (2016): Interdigitation Zone Band Restoration After Treatment of Diabetic Macular Edema, Current Eye Research, DOI: 10.3109/02713683.2015.1113430 To link to this article: http://dx.doi.org/10.3109/02713683.2015.1113430

Published online: 01 Feb 2016.

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Date: 05 February 2016, At: 14:46

CURRENT EYE RESEARCH http://dx.doi.org/10.3109/02713683.2015.1113430

ORIGINAL ARTICLE

Interdigitation Zone Band Restoration After Treatment of Diabetic Macular Edema Satoshi Serizawaa, Kishiko Ohkoshia, Yuko Minowaa, and Kumiko Soejimab

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a Department of Ophthalmology, St. Luke’s International Hospital, Tokyo, Japan; bDepartment of Anesthesiology, St. Luke’s International Hospital, Tokyo, Japan

ABSTRACT

ARTICLE HISTORY

Purpose: To investigate whether the integrity of the interdigitation zone band, the ellipsoid zone band, and the external limiting membrane are reliable markers of treatment outcome in diabetic macular edema (DME). Methods: In this retrospective study, we examined 41 treatment-naïve eyes (38 patients) with DME that were treated with laser therapy, pharmacotherapy, and/or vitrectomy. Best-corrected visual acuity and the integrity of the interdigitation zone band, the ellipsoid zone band, and the external limiting membrane were assessed before treatment and at 3, 6, and 12 months after DME treatment. Results: One year after treatment, the external limiting membrane, ellipsoid zone band, and interdigitation zone band were completely visible in 30 (73.2%), 24 (58.5%), and 2 (4.9%) eyes, respectively. Interdigitation zone band status improved significantly (P = 0.005) 1 year after treatment. The interdigitation zone did not improve in the absence of the ellipsoid zone band. Likewise, ellipsoid zone status did not improve in the absence of the external limiting membrane at any time after treatment. Conclusion: The results of this study show that restoration of the interdigitation zone band constitutes a very sensitive marker of DME treatment outcome when the ellipsoid zone band is visible before treatment.

Received 16 April 2015 Revised 6 September 2015 Accepted 14 October 2015

Introduction Diabetic retinopathy (DR) is the most common complication of diabetes mellitus. This progressive condition induces retinal ischemia, neovascularization, and macular edema. Some DR patients develop diabetic macular edema (DME), which is characterized by swelling of the retina, leading to severe vision loss. Accordingly, the early detection of DME is essential to initiate preventive measures and therapy. Optical coherence tomography (OCT), which noninvasively produces microscopic retinal cross-sectional images, was developed in 1991. OCT images enable the measurement of central macular thickness (CMT) and the evaluation of retinal disease pathogenesis. Since its development, OCT has been used to observe sponge-like retinal swelling, cystoid macular edema (CME), and serous retinal detachment (SRD).1 Additionally, several reports have shown a correlation between macular edema subtype and treatment efficacy.2–5 Technological advances in OCT systems have led to the development of time-domain OCT, which produces high-resolution images. These advances have allowed identification of the photoreceptor ellipsoid zone (EZ) band and the retinal pigment epithelium (RPE).6 In 2006, spectral domain (SD)-OCT was developed to produce ultra-high-resolution retinal images, which made it possible to visualize detailed morphological retinal changes. Imaging studies with SD-OCT have revealed a correlation between EZ band integrity and vision prognosis in eyes with DME.7 Other studies have also shown that the integrity of the EZ band and the external limiting membrane (ELM), which is CONTACT Satoshi Serizawa © 2016 Taylor & Francis

[email protected]

KEYWORDS

Diabetic macular edema; diabetic retinopathy; ellipsoid zone; interdigitation zone; optical coherence; tomography

located at the inner surface of the EZ band, is highly correlated with best-corrected visual acuity (BCVA).8–10 The interdigitation zone (IDZ) band, which is located between the EZ and the RPE, was first observed in 2005.11,12 Since then, studies have shown that IDZ band integrity correlates with BCVA in eyes with retinal vein branch occlusion,13 macular hole,14,15 and acute zonal occult outer retinopathy.16 Additionally, one study demonstrated that the IDZ band status was closely associated with visual acuity in eyes with DME.17 However, the IDZ band has not been specifically examined both before and after treatment of DME. Therefore, the present study evaluated the impact of DME treatment on the integrity of the IDZ band, the EZ band, and the ELM using SD-OCT, as well as any correlation with the DME pattern, BCVA, or treatment type.

Materials and methods The study was conducted in accordance with the tenets of the Declaration of Helsinki. We certify that all applicable institutional and governmental regulations concerning the ethical use of human volunteers were followed during this research. This study was approved by the institutional review board of St. Luke’s International Hospital (Tokyo, Japan). Patients Medical records from 93 consecutive patients with DME who were treated for the first time between December 2009 and

Department of Ophthalmology, St. Luke’s International Hospital, 9-1 Akashicho, Chuo, Tokyo, Japan.

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August 2012 at St. Luke’s International Hospital in the Department of Ophthalmology were examined. Data from 41 eyes of 38 patients were ultimately included in analyses. All patients were examined using SD-OCT both before and after treatment. The exclusion parameters were insufficient SD-OCT image quality (signal strength < 5), vitreous hemorrhage, severe cataract (Emery–Little classification > 3), additional retinal disease (e.g., central or branch retinal vein occlusion), prior DME treatment, or a short ( 600 µm), and in patients with posterior hyaloid traction. In cases where patients were classified into different BCVA categories during the observation period, different treatments were performed than those that were initially used. A total of 51 eyes were treated with direct photocoagulation (for microaneurysms), micropulse laser, or grid laser. STTA and intravitreal anti-VEGF agents were administered to 22 and 29 eyes, respectively, and 18 eyes underwent vitrectomy. Some eyes received multiple types of treatment. BCVA values before treatment and at 3, 6, and 12 months after treatment were 0.463 ± 0.437 (Snellen equivalent: 20/58, range: −0.079 to 1.700), 0.350 ± 0.316 (Snellen equivalent: 20/ 45, range: −0.079 to 1.155), 0.384 ± 0.366 (Snellen equivalent: 20/48, range: −0.079 to 1.301), and 0.343 ± 0.364 (20/40, range: −1.000 to 0.602), respectively, and were significantly improved

at 1 year after treatment (P < 0.001). Additionally, mean CMT before treatment and at 3, 6, and 12 months after treatment were 433.3 ± 158.5 µm (range: 133–1002 µm), 364.9 were 433m (range: 188–706 µm), 375.6 ± 124.8 µm (range: 192–711 µm), and 346.5 ± 112.2 µm (range: 146–640 µm), respectively, and had significantly decreased 1 year after treatment (P = 0.001). No eyes had a laser spot within 1 mm of the central fovea according to SD-OCT 1 mm line scans. Before treatment, the ELM and EZ bands were both visible in most (>85%) eyes, and completely visible in 65.8 and 53.7% of eyes, respectively. In contrast, only a disrupted IDZ band was visible in 36.3% of eyes. The treatment did not affect the repartition of completely visible/disrupted/absent ELM (P = 0.771) or EZ bands (P = 0.462). In contrast, the number of visible IDZ bands doubled to 63.4%, and two eyes presented a completely visible line (P = 0.005) after treatment (Table 2). These data suggest that the restoration of the IDZ band is a very sensitive marker of treatment outcome in DME patients. Previous studies have shown that IDZ band recovery occurs after EZ recovery and EZ band recovery occurs after ELM recovery in eyes with postoperative macular holes. Therefore, we investigated the correlation between IDZ and EZ, and between EZ and ELM in DME. Improvements in the EZ band at 3, 6, and 12 months following treatment were noted in one (3.7%), two (8.7%), and three eyes (7.4%), respectively, in the completely visible ELM group before treatment; in no, three (33.3%), and six eyes (60%), respectively, in the disrupted ELM group before treatment; and in no, no, and no eyes, respectively, in the absent ELM group before treatment (Table 3). Improvements in the IDZ band at 3, 6, and 12 months after treatment were noted in three (14.2%), one (6.3%), and seven eyes (31.8%), respectively, in the completely visible EZ band before treatment; in one (7.7%), one (7.7%), and seven eyes (50%), respectively, in the disrupted EZ band group before treatment; and in no, no, and no eyes, respectively in the absent EZ band group

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Table 2. External limiting membrane (ELM), ellipsoid zone (EZ), and interdigitation zone (IDZ) status before and 1 year after treatment for diabetic macular edema. After treatment (3 mo/ 6 mo/ 1 y)

Before treatment

ELM EZ band IDZ band

Completely visible, eyes (%) 27 (65.8)

Disrupted, eyes (%) 10 (24.3)

Absent, eyes (%) 4 (9.8)

22 (53.7)

14 (34.1)

5 (12.2)

15 (36.6)

26 (63.4)

0

Completely visible, eyes (%) 26 (65.0) /25 (69.4) /30 (73.2) 22 (55.0) /18 (43.9) /24 (58.5) 0 /1 (2.8) /2 (4.9)

Disrupted, eyes (%) 10 (25.0) /7 (19.4) /8 (19.5) 11 (27.5) /11 (26.8) /9 (22.0) 18 (45.0) /16 (43.2) /26 (63.4)

Absent, eyes (%) 4 (10.0) /4 (11.1) /3 (7.3) 7 (17.1) /7 (17.1) /8 (19.5) 22 (55.0) /19 (52.8) /13 (31.7)

*P value 0.77 1 0.46 2 0.00 5

* P-value (baseline to 1 year after treatment) was derived using Fisher’s test.

Table 3. Changes in ellipsoid zone (EZ) and interdigitation zone (IDZ) band status at 3 months, 6 months, and 1 year after treatment for diabetic macular edema.

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Change in EZ band status (3 mo/ 6 mo/ 1 y after treatment) ELM status before treatment

Completely visible Disrupted Absent

EZ status before treatment

Completely visible

Disrupted Absent

Improvement, 1 /2 /2 0 /3 /6 0 /0 /0

eyes (%) (3.7) (8.7) (7.4)

Stable, 25 /15 /18 8 /5 /3 3 /4 /3

(33.3) (60)

eyes (%) (92.6) (65.2) (66.6) (88.9) (55.6) (30) (75) (100) (75)

Absent, 1 /6 /7 1 /1 /1 1 /0 /1

eyes (%) (3.7) (26.1) (25.9) (11.1) (11.1) (10) (25) (25)

Change in IDZ band status (3 mo/ 6 mo/ 1 year after treatment) Improvement, eyes (%) Stable, eyes (%) Deterioration, eyes (%) 3 (14.2) 21 (8.8) 0 /1 (6.3) /14 (87.5) /1 (6.3) /7 (31.8) /14 (63.6) /1 (4.5) 1 (7.7) 12 (92.3) 0 /1 (7.7) /11 (84.6) /1 (7.7) /7 (50) /7 (50) /0 0 5 (100) 0 /0 /5 (100) /0 /0 /5 (100) /0

ELM = external limiting membrane.

before treatment (Table 3). No improvements in EZ band status were observed at 3, 6, and 12 months after treatment when the ELM was absent before treatment. Additionally, no improvements in the IDZ were observed at 3, 6, and 12 months after treatment when the EZ was absent before treatment (Table 3).

The IDZ band was completely visible or disrupted after treatment in 12 eyes (71%) in the laser-treated group and in 8 eyes (53%) in the vitrectomy group (Table 4). IDZ band status was significantly improved in the vitrectomy group after treatment (P = 0.014). A completely visible or disrupted EZ band was noted 1 year after treatment in 17 eyes (42.9%) in the CME

Table 4. External limiting membrane (ELM), ellipsoid zone (EZ), and interdigitation zone (IDZ) band status before and 1 year after different treatments (above). ELM, EZ band, and IDZ band and status before and 1 year after treatment (below), stratified by macular edema subtype. Before treatment (completely visible/ disrupted/absent), eyes Treatment Laser (n = 17) STTA (n = 8) Vitrectomy (n = 15) Macular edema subtype SRD (n = 7) CME (n = 21) CME + SRD (n = 9)

After treatment (completely visible/ disrupted/absent), eyes

ELM

EZ

IDZ

ELM

EZ

IDZ

14/3/0 6/2/0 6/5/4

3/13/1 4/3/1 4/8/3

0/9/8 0/5/3 0/1/14

2/15/0 6/2/0 8/4/3

7/9/1 6/1/1 8/1/6

2/10/5 0/6/2 0/8/7

4/1/2 17/3/1 4/4/1

3/1/3 14/5/2 3/5/1

0/1/6 0/11/10 0/3/6

4/1/2 17/3/1 6/3/0

3/1/3 14/4/3 4/3/2

1/2/4 1/16/4 0/5/4

STTA = sub-Tenon triamcinolone acetonide injection; SRD = serous retinal detachment; CME = cystoid macular edema.

CURRENT EYE RESEARCH

group, 3 eyes (81.0%) in the SRD group, and 5 eyes (55.6%) in the CME+SRD group (Table 4). Univariate analyses showed significant correlations between BCVA after treatment and ELM, EZ, and IDZ status before treatment. An improvement in OCT line integrity was also associated with a better post-treatment BCVA (all P < 0.001). Posttreatment BCVA was also dependent upon pretreatment BCVA macular edema subtype, DR stage, and CMT. Multivariate analysis showed that post-treatment BCVA was correlated with BCVA and EZ status before treatment (P = 0.047).

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Discussion The OCT device has become a vital tool in the diagnosis and treatment of DME. The OCT directs beams of infrared light at the retina to generate cross sectional images of the retinal layers. The photoreceptor outer segment is a cylindrical structure that contains visual pigments (e.g., rhodopsin) and is located at the tip of each light-sensing neuron. When light is absorbed by the outer segment, a series of reactions occur that lead to cell hyperpolarization and electrical signal transduction. Therefore, proper photoreceptor outer segment function is essential to achieving high-quality vision. In 2004, Ko et al.6 reported that OCT images of the inner/outer segment junction line reflect EZ integrity. However, Spaide et al.18 more recently argued that this image feature directly represents the EZ, which is now generally agreed upon.19 The IDZ band, first detected with SD-OCT, is believed to represent cone outer segment terminals located between the EZ band and the RPE. Cone outer segment length is approximately half that of the rod, and its terminal is surrounded by the RPE. In 2011, Spaide et al.18 reported that the IDZ band represents RPE microvilli that surround cone outer segments. This finding was confirmed in a subsequent study.19 Itoh et al.20 reported that the IDZ band in most epiretinal membrane patients 1 year after surgery had a defect less than 1000 µm in length in the central fovea. In a different study, Itoh et al.15 also reported that the IDZ band recovered in about half of patients after macular hole repair surgery.15 In contrast, more than half of our DME patients did not have IDZ band recovery. Therefore, IDZ recovery seems to occur less frequently in eyes with DME than in eyes with epiretinal membrane or a macular hole. Previous studies have shown that IDZ band recovery is delayed in eyes with postoperative macular holes and that longer IDZ band recovery times lead to poorer visual outcomes.15 Mitamura et al.21 also reported that macular holes led to IDZ band destruction, followed by EZ band destruction, and, finally, ELM destruction. Recovery occurred in the opposite order. Our findings indicate that the EZ band does not recover after DME treatment when the ELM is absent before treatment. Similarly, in eyes where the EZ had disappeared, the IDZ did not recover after treatment. The IDZ recovered only in the presence of an intact ELM and EZ. Therefore, it is possible that the state of the EZ and ELM determines the extent of IDZ band recovery in eyes with DME. In this study, the IDZ band status of patients was significantly improved in the vitrectomy-treated group.

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In 2013, Itoh et al.17 reported that ELM, EZ, and IDZ band status are all correlated with BCVA in eyes with DME. Our research also indicated a relationship between pretreatment EZ band status and BCVA 1 year after treatment (P = 0.047). A better EZ band pretreatment status was associated with better BCVA following treatment. However, multivariate analysis did not show a significant relationship between pretreatment ELM or IDZ band status and BCVA 1 year after treatment. Most of our DME patients had an absent or incomplete IDZ band. Therefore, only a small number of patients had an intact IDZ band, making it difficult for this correlation to achieve statistical significance. We also conclude that pretreatment SD-OCT imaging is useful for evaluating EZ band status and predicting posttreatment visual outcomes following DME treatment. The present study had several limitations. First, marked destruction of the retinal layers occurs in the majority of DME cases. Together with the effect of artifact-causing hard exudates and intraretinal hemorrhage, this can impede OCT imaging and disease diagnosis. The IDZ is the deepest of the three photoreceptor OCT lines and is most affected by these imaging artifacts. In addition, retinal thinning due to high-degree myopia could make locating the IDZ difficult, although no eyes in this study were highly myopic. Moreover, OCT images do not completely reflect actual histopathology. Therefore, OCT lines may be graded as completely visible even when underlying structures are not complete. In the current study, only two perpendicular lines crossing the macular center were examined. However, characteristics of other parts of the macula may be important, and these could have interfered with the accurate prediction of visual treatment outcomes. Last, this study included eyes that had received different types of DME treatment: ideally, the study should have included only patients undergoing the same therapy. However, examining a variety of therapies makes our results more universally applicable. As noninvasive retinal imaging techniques and other diagnostic tools advance, broader and more detailed photoreceptor evaluations may be achievable. This will improve our ability to diagnose and treat DME and other retinal diseases. Restoration of the IDZ band constitutes a very sensitive marker of DME treatment outcome when the EZ band is visible before treatment.

Declaration of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

References 1. Otani T, Kishi S, Maruyama Y. Patterns of diabetic macular edema with optical coherence tomography. Am J Ophthalmol 1999;127:688–693. 2. Otani T, Kishi S. Tomographic assessment of vitreous surgery for diabetic macular edema. Am J Ophthalmol 2000;129:487–494. 3. Otani T, Kishi S. Tomographic findings of foveal hard exudates in diabetic macular edema. Am J Ophthalmol 2001;131:50–54. 4. Otani T, Kishi S. A controlled study of vitrectomy for diabetic macular edema. Am J Ophthalmol 2002;134:214–219.

Downloaded by [La Trobe University] at 14:46 05 February 2016

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5. Yamaguchi Y, Otani T, Kishi S. Resolution of diabetic cystoid macular edema associated with spontaneous vitreofoveal separation. Am J Ophthalmol 2003;135:116–118. 6. Ko TH, Fujimoto JG, Duker JS, Paunescu LA, Drexler W, Baumal CR et al. Comparison of ultrahigh- and standard-resolution optical coherence tomography for imaging macular hole pathology and repair. Ophthalmology 2004;111:2033–2043. 7. Maheshwary AS, Oster SF, Yuson RM, Cheng L, Mojana F, Freeman WR et al. The association between percent disruption of the photoreceptor inner segment/outer segment and visual acuity in diabetic macular edema. Am J Ophthalmol 2010;150:63–67. 8. Otani T, Yamaguchi Y, Kishi S. Correlation between visual acuity and foveal microstructural changes in diabetic macular edema. Retina 2010;30:774–780. 9. Sakamoto A, Nishijima K, Kita M, Oh H, Tsujikawa A, Yoshimura N. Association between foveal photoreceptor status and visual acuity after resolution of diabetic macular edema by pars plana vitrectomy. Graefes Arch Clin Exp Ophthalmol 2009;247:1325–1330. 10. Chhablani JK, Kim JS, Cheng L, Kozak I, Freeman W. External limiting membrane as a predictor of visual improvement in diabetic macular edema after pars plana vitrectomy. Graefes Arch Clin Exp Ophthalmol 2012;250:1415–1420. 11. Sandberg MA, Brockhurst RJ, Gaudio AR, Berson EL. The association between visual acuity and central retinal thickness in retinitis pigmentosa. Invest Ophthalmol Vis Sci 2005;46:3349–3354. 12. Srinivasan VJ, Monson BK, Wojtkowski M, Bilonick RA, Gorczynska I, Chen R, et al. Characterization of outer retinal morphology with high-speed, ultrahigh-resolution optical coherence tomography. Invest Ophthalmol Vis Sci 2008;49:1571–1579.

13. Murakami T, Tsujikawa A, Ohta M, Miyamoto K, Kita M, Watanabe D, et al. Photoreceptor status after resolved macular edema in branch retinal vein occlusion treated with tissue plasminogen activator. Am J Ophthalmol 2007;143:171–173. 14. Itoh Y, Inoue M, Rii T, Hiraoka T, Hirakata A. Correlation between length of foveal cone outer segment tips line defect and visual acuity after macular hole closure. Ophthalmology 2012;119:1438–1446. 15. Itoh Y, Inoue M, Rii T, Hiraoka T, Hirakata A. Significant correlation between visual acuity and recovery of foveal cone microstructures after macular hole surgery. Am J Ophthalmol 2012;153:111–119. 16. Wakazono T, Ooto S, Hangai M, Yoshimura N. Photoreceptor outer segment abnormalities and retinal sensitivity in acute zonal occult outer retinopathy. Retina 2013;33:642–648. 17. Ito S, Miyamoto N, Ishida K, Kurimoto Y. Association between external limiting membrane status and visual acuity in diabetic macular oedema. Br J Ophthalmol 2013;97:228–232. 18. Spaide RF, Curcio CA. Anatomical correlates to the bands seen in the outer retina by optical coherence tomography: literature review and model. Retina 2011;31:1609–1619. 19. Staurenghi G, Sadda S, Chakravarthy U, Spaide RF. Proposed lexicon for anatomic landmarks in normal posterior segment spectral-domain optical coherence tomography: the IN•OCT consensus. Ophthalmology 2014;121:1572–1578. 20. Itoh Y, Inoue M, Rii T, Hirota K, Hirakata A. Correlation between foveal cone outer segment tips line and visual recovery after epiretinal membrane surgery. Invest Ophthalmol Vis Sci 2013;54:7302–7308. 21. Mitamura Y, Mitamura-Aizawa S, Katome T, Naito T, Hagiwara A, Kumagai K, et al. Photoreceptor impairment and restoration on optical coherence tomographic image. J Ophthalmol 2013;2013:518170.

Interdigitation Zone Band Restoration After Treatment of Diabetic Macular Edema.

To investigate whether the integrity of the interdigitation zone band, the ellipsoid zone band, and the external limiting membrane are reliable marker...
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