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 Table of Contents  
ORIGINAL ARTICLE
Year : 2013  |  Volume : 1  |  Issue : 1  |  Page : 7-13

The relationship between photoreceptor IS/OS junction changes and visual acuity in diabetic macular edema


Department of Ophthalmology, Kaser Al Aini Medical School, Cairo University Cairo, Egypt

Date of Web Publication9-Dec-2013

Correspondence Address:
Nehal M Samy El Gendy
Lecturer of Ophthalmology Cairo University, Egypt 43 Gameat El Dewal Street, Giza
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2347-5617.122817

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  Abstract 

Purpose: To evaluate the integrity of the photoreceptor inner segment and outer segment (IS/OS) junction using spectral-domain optical coherence tomography (SD OCT) in patients with diabetic macular edema and to correlate the relationship between the integrity of the IS/OS junction and visual acuity. Design: Observational, prospective study. Materials and Methods: Forty eyes of 22 diabetic patients having diabetic macular edema. The authors performed spectral-domain optical coherence tomography in all eyes before treatment, 1month and 6 months after treatment. Central subfield thickness was defined as the average retinal thickness of the central 1-mm scanned area. The length of disruption of the inner and outer segments of the photoreceptors in the fovea were measured and graded according to their length as follows: Grade 0: Intact IS/OS line (no disruption at all), grade 1: Mild disruption (<400 μm). Grade 2: Moderate disruption (>400 μm but <1400 μm), Grade 3: Severe disruption (>1400 μm )or completely lost. Results: At the baseline, there was no correlation between the visual acuity (VA) and grade of defect (r = 0.214, P-value = 0.190). After 1 month and 6 months of treatment, there was a correlation between the VA and the grade of the defect (r = 0.538, P-value < 0.001) (r =0.603, P-value < 0.001), respectively. There was no significant association between the improvement in the IS/OS and final VA (P-value < 0.385). The mean change in VA from base line to 1 month in those who showed improvement in the defect was better than those in the nonimproved group (P-value = 0.001), and the mean change in the VA values from base line to 6 months in the improved group was better than those in the non improved group (P-value = 0.001). Conclusions: SD OCT showed that the integrity of the inner and outer segments of the photoreceptors was correlated with best-corrected visual acuity only 1 and 6 month after treatment, but not before treatment, so the correlation was not absolute.

Keywords: Diabetic macular edema, IS/OS line, SD OCT


How to cite this article:
Samy El Gendy NM, Arfeen SA, Rafaat KA, Sheta SM. The relationship between photoreceptor IS/OS junction changes and visual acuity in diabetic macular edema. Egypt Retina J 2013;1:7-13

How to cite this URL:
Samy El Gendy NM, Arfeen SA, Rafaat KA, Sheta SM. The relationship between photoreceptor IS/OS junction changes and visual acuity in diabetic macular edema. Egypt Retina J [serial online] 2013 [cited 2020 Mar 30];1:7-13. Available from: http://www.egyptretinaj.com/text.asp?2013/1/1/7/122817


  Introduction Top


Macular edema is a major cause of visual deterioration in diabetic retinopathy. Several therapeutic modalities, including grid laser photocoagulation, [1] vitrectomy, [2] intravitreal injection of ranibizumab, [3] or triamcinolone acetonide [4] have been investigated. The efficacies of these therapies have been evaluated by best-corrected visual acuity (BCVA) and macular thickness measurement using optical coherence tomography (OCT). A correlation between BCVA and the OCT-measured macular thickness has been reported but its significance was variable. [5] A marked decrease in macular thickness after therapy may not improve BCVA, which suggests that macular thickness is only one of several factors to affect BCVA. Recent technological advances in OCT have enabled identification of the external limiting membrane (ELM) and the junction between the inner and outer segments (IS/OS) of the photoreceptors. Several articles have described association between the integrity of the foveal photoreceptor layer and the BCVA in macular diseases. [6],[7],[8],[9]

In this study, we assessed the changes of the IS/OS in diabetic macular edema (DME) before and after treatment, and investigated the correlation between these changes and BCVA using spectral-domain OCT.


  Materials and Methods Top


This is a prospective observational study that includes 40 eyes of 22 diabetic patients having DME. Patients were recruited from the outpatient clinic of Kasr El-Aini Hospital - Cairo University in the period from June 2011 to January 2012. OCT was done at Bostan Diagnostic Eye Center. This study included diabetic patients with clinically significant DME diagnosed by slit-lamp biomicroscopy, defined according to the ETDRS. Exclusion Criteria include (1) corneal opacities or any media opacity; (2) moderate to dense lens opacities; (3) history of intraocular inflammation such as anterior or posterior uveitis; (4) eyes with other conditions that can cause macular thickening such as venous occlusion, epiretinal membrane, and/or vitreomacular traction; (5) macular ischemia diagnosed as areas of macular capillary nonperfusion by fundus Fluorescein angiography. Thorough history taking and complete ophthalmological examination was done. Visual acuity was measured by Snellen's chart then converted to Log MAR. OCT (optical coherence tomography) was performed. Using SD OCT RTvue (model RT100, Optovue, Inc., Fremont, CA), we used vertical and horizontal 6-mm line scan passing through the central fovea, the IS/OS line was evaluated considering its continuity in the central fovea, any disruption in the line, which was defined as loss of back reflection line, was measured by manual caliber, the scores for the horizontal and vertical scans were then averaged for each eye and graded according to its length as follows: (1) Grade 0: Intact IS/OS line (no disruption at all); (2) Grade 1: Mild disruption (<400μm); (3) Grade 2: Moderate disruption (>400 μm but <1400 μm); (4) Grade 3: Severe disruption (>1400 μm)or completely lost. We measured the central subfield foveal thickness, defined as the average retinal thickness (RT) of 1-mm central scanned area, using macular map (MM5) that is 5 × 5 mm square grid centered on fixation. The grid is composed of 17 horizontal and 17 vertical line scans. Both the horizontal and the vertical lines are formed of: (1) 11 lines with 5 mm scan length and 0.5 mm interval, (2) six lines with 3 mm scan length and 0.5 mm interval. OCT was done to all patients before treatment, at 1 and 6 months of treatment.

Statistical analysis

Data management and analysis were performed using Statistical Analysis Systems. Numerical data were summarized using means and standard deviations or median and ranges. Categorical data were summarized as percentages. Comparisons between the two groups with respect to numeric variables were done by Mann-Whitney test, a nonparametric test equivalent to the Student's t test. Kruskal-Wallis test followed by the post hoc Dunn test for nonparametric data was performed to compare more than two groups with respect to numeric variables. The chi-square test was used to compare between the groups with respect to categorical data. The Spearman correlation for nonparametric data was used (Dawson and Trapp, 2001) to assess the degree of association between the numeric variables All P-values are two-sided. P-values < 0.05 were considered significant.


  Results Top


Optical coherence tomography scans of 55 eyes of 33 patients were done, 15 eyes were excluded as they did not complete their follow up, and so 40 eyes of 22 patients were included in the statistical analysis, OCT scans were done at baseline, one month and 6 months.

The patients' age was ranged from 34 to 68 years with mean age value 56 ± 7.4 years, 11 males (50%), 11 females (50%), the duration of diabetes ranged from 4 to 20 years with a mean of 12 ± 5.2 years, 15 patients (68.2%) are on insulin treatment, 7 patients (31.8%) are on oral treatment. Six patients are hypertensive (27.3%), 16 patients are not known to be hypertensive (72.7%) [Table 1].
Table 1: Characteristics of the patients

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Nine eyes received argon laser treatment only, six eyes received diode laser, three eyes received intravitreal bevacizumab injection(monthly for 3 months then PRN), one eye received argon laser followed by intravitreal triamcinolone injection, three eyes received intravitreal bevacizumab followed by argon laser, one eye received micropulse diode laser followed by intravitreal triamcinolone injection, four eyes received intravitreal triamcinolone injection, nine eyes received intravitreal triamcinolone injection followed by argon laser, oen eye received intravitreal triamcinolone injection followed by argon laser then intravitreal triamcinolone injection again, three eyes did not receive any treatment [Table 2].
Table 2: Type of treatment of macular edema received by the patients

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OCT scanning was done at baseline, after 1 month of treatment and 6 months. We measured the central subfield foveal thickness, defined as the average RT of 1-mm central scanned area, using macular maps (MM5), the IS/OS line was evaluated considering its continuity, any disruption in the line, was measured by manual caliber and graded according to its length [Figure 1].
Figure 1: Grading of the defect (a) intact, (b) mild disruption (304 μm), (c) moderate disruption (1200&956;m), (d) severe disruption (1950μm)

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In our study, IS/OS line was intact in 16 eyes, mildly disrupted in four eyes, moderately disrupted in 10 eyes and severely disrupted in 10 eyes before treatment. For statistical purposes we combined the mild and moderate groups in one group. At baseline the median of the defect was 407μm (ranged from 0 in the intact group to 1800 in the completely lost group). The BCVA ranged from (1.5 to 0.00 log MAR) with mean value of 0.62 ± 0.34. The central subfield foveal thickness (CSFT) ranged from 241 to 874 μm with a mean value of 387 ± 335 μm [Table 3].
Table 3: Statistical values of the parameters at the baseline

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Where BCVA: Best corrected visual acuity; CSFT: Central subfield foveal thickness; IS: Inner segment; OS: Outer segment

The values of visual acuity of the intact group were not statistically different from those of the mildly and moderately disrupted group, but statistically different from the severely disrupted group (P value 0.019) [Figure 2].
Figure 2: The mean values of VA in each group at baseline (signifi cant difference between intact group and severely disrupted (P-value = 0.019)

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There was a weak correlation between the visual acuity at the baseline and the CSFT (r = 0.458) (P-value 0.003) [Figure 3], and no correlation between the VA and grade of defect after controlling for the effect of central subfield foveal thickness (r = 0.214, P-value 0.190) [Figure 4].
Figure 3: Correlation between VA and macular thickness at baseline (r = 0.458)

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{Figure 4}

After 1 month of treatment, the IS/OS junction line was intact in 17 (42.5%) eyes, moderately disrupted in 10 eyes (25%), and severely lost in 13 eyes (32.5%) The median of the defect was 263 μm (ranged from 0 in the intact group to 1800 in the completely lost), the BCVA ranged from (1.5 to 0.00 log MAR) with mean value of 0.54 ± 0.5, the central subfield foveal thickness ranged from 241 to 874μm with mean value 316 ± 87μm [Table 4].
Table 4: Statistical values of the parameters after 1 month

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Where BCVA: Best corrected visual acuity; CSFT: Central subfield foveal thickness; IS: Inner segment; OS: Outer segment

The values of visual acuity of the intact group were not statistically different from those of the moderately disrupted group, but significant statistical difference was found between it and the severely disrupted group (P-value = 0.001)

There was a very weak correlation between the visual acuity and CSFT (r = 0.312) which was not significant (P-value = 0.05), and moderate correlation between the VA and the grade of the defect (r = 0.538, P-value < 0.001)

After 6 months of treatment, the IS/OS junction line was intact in 19 (47.5%) eyes compared to 16 eyes at baseline, the VA of the eyes that showed improvement of the defect improved in two of them that received micropulse diode laser and did not change in one eye that had undergone argon laser treatment. The IS/OS line was moderately disrupted in 10 eyes (25%) and severely disrupted in 11 eyes (27.5%). The median of the defect was 139 ± 783 μm (ranged from 0 in the intact group to 1800 in the completely lost), the BCVA ranged from (1.5 to 0.00 log MAR) with the mean value of 0.52 ± 0.36, the central subfield foveal thickness ranged from 160 to 648μm with the mean value 315 ± 106 μm [Table 5].
Table 5: Statistical values of the parameters after 6 months

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Where BCVA: Best corrected visual acuity; CSFT: Central subfield foveal thickness; IS: Inner segment; OS: Outer segment

The values of visual acuity of the intact group were statistically significantly different from those of the moderately disrupted group, and those of the severely disrupted group (P-value < 0.001).

There was a weak correlation between the visual acuity and CSFT (r = 0.468) (P-value = 0.002), moderate correlation between the defect and VA (r = 0.603, P-value < 0.001).

During the follow up, 21 eyes showed improvement in the VA, eight eyes showed worsening while 11 eyes showed no change [Table 6].
Table 6: Frequency of improvement in visual acuity

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Eleven eyes showed improvement in the IS/OS defect, seven eyes worsening in the defect, 21 eyes with no change, one eye showed worsening in the defect after one month then it returns to its base line grade after 6 months [[Table 7] and [Figure 5].
Figure 5: Change of IS/OS status through the follow up period. (A) This patient showed mild disruption (B) which changed to severe disruption after 1month of treatment (B) then returned to mild disruption after 6 months

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Table 7: Frequency of improvement of the defect

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We found no significant association between the improvement of the IS/OS defect and improvement in the VA, as among those who showed improvement in the IS/OS defect 33.3% only showed improvement in VA, while those who did not show improvement in the defect 21.1% showed improvement in the VA, (P-value = 0.385) (for statistical purposes we considered the worsening and no change as one group named not improved) [Table 8].
Table 8: Cross tabulation between the improvement of the defect and the improvement in the VA

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The mean change in the VA values from base line to 1 month and from baseline to 6 month in the improved group (who showed improvement in the defect) was significantly different from those in the non improved group (P-value = 0.001) [Figure 6] and [Table 9].
Figure 6: Mean change of visual acuity through followup

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Table 9: The mean change of VA from base line to 1 month and from baseline to 6 months

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  Discussion Top


Diabetic macular edema (DME) is the leading cause of visual loss in diabetic individuals. The use of the OCT was incorporated in the routine work of the ophthalmologists after studies demonstrated its collaboration on the detection of the disease. Beside confirming diagnostic impressions, the OCT monitors the pharmacological treatment of the macular edema and follows its progression. [10]

With the improved visualization of retinal architecture after introducing the SD OCT, many clinical studies have used this imaging technique to evaluate the effectiveness of various treatment modalities. Through these studies, authors have found that some eyes with DME have poor visual outcomes despite complete resolution of edema. [11] Several studies showed that many factors influence visual function in eyes with DME, including morphologic pattern of edema (cystic or diffuse retinal thickening), duration of retinal edema, retinal perfusion, total retinal volume, vitreomacular interface abnormalities, [12] macular ischemia, photoreceptor dysfunction and accumulated subfoveal hard exudates. [13] Integrity of the photoreceptor inner segment-outer segment (IS/OS) junction has been shown to correlate well with VA in cross sectional studies of patients with DME. In our prospective study, we found that the mean value of visual acuity in the intact group (0.48 ± 0.28 log MAR) was better than the severely disrupted group (0.86 ± 0.42 log MAR) (P-value = 0.19); however, there was no correlation between the VA and grade of defect after controlling for the effect of central subfield foveal thickness (r = 0.214, P-value = 0.190). After 1 month of treatment, the mean value of VA in the intact group (0.35 ± 0.19 log MAR) was significantly better than that in the severely disrupted group (0.8 ± 0.39) (P-value = 0.001); however no statistically significant difference was found between the intact group and the moderately disrupted group. One month post-treatment, correlation between the VA and the grade of the defect (r = 0.538, P-value < 0.001) was recorded. After 6 months, the mean value of the visual acuity in the intact group (0.28 ± 0.19 log MAR) was better than the moderately disrupted group (0.55 ± 0.12 log MAR), and better than the severely disrupted group (0.92 ± 1.00 log MAR) (P-value < 0.001), we also found moderate correlation between the defect in the IS/OS junction and VA (r = 0.603, P-value < 0.001).

A retrospective study by Anjali et al., found that disruption of the IS/OS junction was a very critical aspect in prediction of final visual acuity in patients with DME; they found a strong relationship between macular volume and percent disruption of the IS/OS junction and a borderline significance was found between macular volume and visual acuity. They used the macular volume to represent macular thickness referring to what is reported by the Diabetic Retinopathy Clinical Research Network that total macular volume may be used when macular edema is more diffuse and represents a more global measurement of macular edema. [14]

These results are consistent with ours; however, in our study we assessed the RT by the central subfield foveal thickness, defined as the average RT of 1-mm central scanned area, using macular maps (MM5). Browning et al. suggested to assess the RT by using the central subfield macular thickness (CSFT) due to high reproducibility, being based on more scans than the central foveal thickness (CFT), and having higher correlation with other measures of the central macula; [15] in our study we found a weak correlation between the visual acuity and the CSFT. When we studied the effect of the improvement of the IS/OS line defect on the final VA, we found that there was no significant association between both (P-value = 0.385). As among those who had improvement in the defect, 33.3% only improved in VA. On the other hand, 21.1% of those who did not show improvement in the defect still showed improvement in the VA (P-value = 0.385). The mean change in VA from base line to 1 month in those who showed improvement in the defect was better than those in the nonimproved group (P-value = 0.001), and the mean change in the VA values from base line to 6 months in the improved group was better than those in the non improved group (P-value = 0.001). These results could be correlated with a recent prospective study done by Domalpally et al. to assess associations between visual acuity (VA) and the status of the photoreceptor IS/OS junction in a subset of patients with BRVO during the follow-up period; however, they showed a significant association between change in IS/OS status and change in VA from baseline to 1 year. They also reported that the IS/OS status that returned to normal was associated with improvement in VA and vice versa. They observed that the change in IS/OS status had a stronger correlation with change in VA than change in central RT.

Although our study and their study had almost the same sample size (42 eyes), they found strong correlation between the change of the status of IS/OS and visual acuity that can be explained by the difference in the pathology between DME and macular edema due to vein occlusion; another possible explanation is image quality issues due to the presence of more hemorrhage and hard exudates in vein occlusion than in diabetic fundus. [16]

Our study was limited by a small sample size, also we only used the horizontal and vertical line scans through the central fovea; therefore, the IS/OS that was not included on these scan lines was not evaluated. Despite the limitations of our study, our results have potentially important implications for monitoring DME and using OCT findings as a predictor for visual acuity in clinical trials and in clinical practice. This might be important because of its prospective nature as most of the previous studies have not evaluated the association between the IS/OS and BCVA in eyes with macular edema rather than after resolution of macular edema.

In conclusion, spectral-domain OCT is a useful tool to evaluate foveal microstructural changes, including the IS/OS line. Best-corrected visual acuity was more affected by the integrity of the IS/OS than CSFT in DME.

 
  References Top

1.Bresnick GH. Diabetic maculopathy: A critical review highlighting diffuse macular edema. Ophthalmology 1983;90:1301-17.  Back to cited text no. 1
    
2.Lewis H, Abrams GW, Blumenkranz MS, Campo RV. Vitrectomy for diabetic macular traction and edema associated with posterior hyaloidal traction. Ophthalmology 1992;99:753-75.  Back to cited text no. 2
    
3.Massin P, Bandello F, Garweg JG, Hansen LL, Harding SP, Larsen M, et al. Safety and efficacy of ranibizumab in diabetic macular edema (RESOLVE study): A 12-month, randomized, controlled, double-masked, multicenter phase II study. Diabetes Care 2010;33:2399-405.  Back to cited text no. 3
    
4.Martidis A, Duker JS, Greenberg PB, Rogers AH, Puliafito CA, Reichel E, et al. Intravitreal triamcinolone for refractory diabetic macular edema. Ophthalmology 2002;109:920-7.  Back to cited text no. 4
    
5.Hee MR, Puliafito CA, Duker JS, Reichel E, Coker JG, Wilkins JR, et al. Topography of diabetic macular edema with optical coherence tomography. Ophthalmology 1998;105:360-70.  Back to cited text no. 5
    
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;111:2033-43.  Back to cited text no. 6
    
7.Matsumoto H, Kishi S, Otani T, Sato T. Elongation of photoreceptor outer segment in central serous chorioretinopathy. Am J Ophthalmol 2008;145:162-8.  Back to cited text no. 7
    
8.Aizawa S, Mitamura Y, Baba T, Hagiwara A, Ogata K, Yamamoto S. Correlation between visual function and photoreceptor inner/outer segment junction in patients with retinitis pigmentosa. Eye 2009;23:304-8.  Back to cited text no. 8
    
9.Sayanagi K, Ikuno Y, Soga K, Tano Y. Photoreceptor inner and outer segment defects in myopic foveoschisis. Am J Ophthalmol 2008;145:902-8.  Back to cited text no. 9
    
10.Browning DJ, Fraser CM. The predictive value of patient and eye characteristics on the course of subclinical diabetic macular edema. Am J Ophthalmol 2008;145:149-54.  Back to cited text no. 10
    
11.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;247:1325-30.  Back to cited text no. 11
    
12.Blumenkranz MS, Haller JA, Kuppermann BD, Williams GA, Ip M, Davis M, et al. Correlation of visual acuity and macular thickness measured by optical coherence tomography in patients with persistent macular edema. Retina 2010;30:1090-4.  Back to cited text no. 12
    
13.Otani T, Kishi S. Tomographic findings of foveal hard exudates in diabetic macular edema. Am J Ophthalmol 2001;131:50-4.  Back to cited text no. 13
    
14.Maheshwary AS, Oster SF, Yuson RM, Cheng L, Mojana F, Freeman WR. The association between percent disruption of the photoreceptor inner segment-outer segment junction and visual acuity in diabetic macular edema. Am J Ophthalmol 2010;150:63-7.  Back to cited text no. 14
    
15.Browning DJ, Apte RS, Bressler SB, Chalam KV, Danis RP, Davis MD, et al. Diabetic Retinopathy Clinical Research Network. Association of the extent of diabetic macular edema as assessed by optical coherence tomography with visual acuity and retinal outcome variables. Retina 2009;29:300-5.  Back to cited text no. 15
    
16.Domalpally A, Peng Q, Danis R, Blodi B, Scott IU, Ip M; SCORE Study Research Group. The SCORE Study Research group. Association of outer retinal layer morphology with visual acuity in patients with retinal vein occlusion: SCORE Study Report 13. Eye 2012;26:919-24.  Back to cited text no. 16
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 5], [Figure 6]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9]



 

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