Vitrectomy for DME Without Macular Traction

In a small trial, the authors test the theory of early vitrectomy for DME.

TAKAO HIRANO, MD · TOSHINORI MURATA, MD, PhD

Treatments for diabetes mellitus and its complications have improved significantly over the past decades, but diabetic retinopathy remains a leading cause of blindness. Nineteen million Americans older than 20 currently have type 2 diabetes,¹ and the International Diabetes Federation estimates that by 2030, 439 million individuals worldwide will have diabetes.²

Proliferative diabetic retinopathy is the most common cause of severe vision loss in patients with diabetes, but diabetic macular edema is the most frequent cause of social blindness.³ The prevalence of DME among patients with type 2 diabetes is 14%,¹ and the 10-year incidence of DME among patients with type 2 diabetes is 25.4%.⁴

Over the past three decades, we have used focal and grid pattern laser photocoagulation,^5,6 intravitreal injections of corticosteroids,^7,8 and most recently, intravitreal injections of drugs that prevent binding of VEGF to treat DME.^9,10 Pars plana vitrectomy effectively treats DME associated with vitreomacular traction,^11,12 but many authors have also reported excellent results following vitrectomy for foveainvolving, diffuse DME without apparent vitreomacular traction.^7,13-25

NEED FOR EVALUATION

Unfortunately, adequately powered and meticulously designed trials to evaluate the efficacy of vitrectomy in eyes without obvious vitreomacular traction have not been performed. The many papers that have failed to show a correlation between resolution of DME and recovery of vision after vitrectomy have further clouded questions regarding efficacy.^20-22

Deterioration of vision in eyes with DME is directly associated with an increase in central macular thickness, but resolution of edema following vitrectomy does not necessarily lead to visual recovery.²¹ Recent reports, however, have suggested that photoreceptor integrity, as determined by spectral-domain optical coherence tomography (SD-OCT),measurements of the external limiting membrane and inner segment/outer segment line continuity, combined with resolution of edema, are important determinants of post-treatment improvement in vision.¹⁶

Figure 1. The correlation between visual acuity and central macular thickness after vitrectomy for DME in the eyes in IS/OS group. The average CMT decreased significantly at one month, rebounded briefly, and then decreased again at four months and thereafter to 12 months. The average VA improvement became significant at seven months and remained through 12 months.

In this study, we evaluated the long-term effect of vitrectomy on the resolution of macular edema and recovery of vision in eyes with DME. We carefully documented monthly decreases in central macular thickness and improvements in visual acuity, and we correlated the preoperative integrity of the IS/OS line with postoperative visual improvement.

SUBJECTS AND METHODS

Between 2011 and 2013, we prospectively studied 38 eyes of 36 patients with DME. Eligible patients had persistent DME despite previous sub-Tenon’s injections of triamcinolone acetonide (20 mg) and focal/grid laser photocoagulation of the macula.

Upon entering the study, all of the patients underwent complete ophthalmologic examinations, which included best-corrected decimal visual acuity, slit-lamp biomicroscopy, indirect ophthalmoscopy, and SD-OCT (Cirrus OCT, Carl-Zeiss, Dublin, CA) examinations. We diagnosed DME by slit-lamp biomicroscopy with a 90 D lens, confirmed by SD-OCT and fluorescein angiography.

We scheduled the patients for monthly examinations through 12 months. We included those we examined at least 10 times in the final data analysis. At each postoperative visit, we measured BCVA and obtained macular SD-OCT images.

All participants provided informed consent, and all eyes underwent PPV with internal limiting membrane peeling. All treatments conformed to the Declaration of Helsinki for research involving human subjects. The Institutional Review Board of Shinshu University in Matsumoto, Japan, approved the study.

Image Grading

One millimeter of central macular thickness (CMT) was the central subfield thickness as calculated by the macular map function of the Cirrus SD-OCT. We expressed the amount of disruption of both the IS/OS and ELM lines for 500 μm from the foveal center as a fraction between 0% (no disruption) and 100% (total loss of the layer in both horizontal and vertical scans). We categorized eyes with at least 30% preservation of the IS/OS lines as IS/OS(+) and those with less than 30% as IS/OS(-).

Surgical Procedures

We performed standard three-port 23-gauge PPV in all eyes. To enable complete removal of the vitreous, we used triamcinolone acetonide to facilitate visualization and created posterior vitreous separation with aspiration. We peeled the ILM from the macula after staining with Brilliant Blue G dye.

Statistical Analysis

We measured visual acuities on the decimal eye chart and converted the values to logMAR for statistical analysis. We evaluated improvements in logMAR VA and decreases in CMT (compared to the preoperative measurements) with one-way ANOVA.

RESULTS

Of the 38 enrolled eyes, 18 (47%) were IS/OS(+), while 20 (53%) were IS/OS(-). The average VA for all 38 eyes at month 12 (20/58, logMAR 0.46±0.45) trended toward better but was not significantly different from baseline (20/113, logMAR 0.75±0.35, P=.07). The average CMT improved significantly by month 12.

For the 18 IS/OS(+) eyes, VA significantly improved from baseline (20/65, logMAR 0.51±0.33) to month 7 (P=.005) and then continued to improve through month 12 (20/22, logMAR 0.04±0.14) (Figure 1). The average CMT decreased significantly at one month (baseline: 546±156 μm, 1 month: 342±21 μm), rebounded briefly, and then decreased again at four months (306±19μm) and thereafter to 12 months (289+64 μm).

Figure 2. Central macular thickness decreased with restoration of normal foveal depression. As DME resolved, the IS/ OS (large arrow) and ELM lines partially regenerated (small arrow).

In subgroup analysis, the four eyes that did not experience improved CMT by month 12 did not experience improvement in vision. Representative longitudinal changes of cross-sectional SD-OCT images are shown in Figure 2. CMT generally decreased, with restoration of the normal foveal depression at 1 month, and as the DME further resolved, the IS/OS and ELM lines partially regenerated.

Among the 20 IS/OS(-) eyes, the average VA did not improve significantly by month 12. In a subgroup analysis, the seven eyes with decreased CMT at month 12 (baseline CMT: 527±175 μm, 12 months: 227±25 μm) did not experience improved VA (baseline VA: logMAR 0.89±0.22, VA at 12 months: logMAR 0.76±0.31). Despite restoration of foveal depression, the IS/OS did not reform, thereby suggesting a permanent loss of photoreceptor integrity (Figure 3).

DISCUSSION

Many physicians believe that resolution of macular edema, as measured by a decrease in CMT, will result in visual recovery. Unfortunately, despite the complete resolution of DME following anti-VEGF injections, corticosteroid injections, laser photocoagulation, or vitrectomy, some eyes do not experience recovery of VA.¹⁴

The reason for this paradox is not completely understood, but photoreceptor damage, as identified by loss of IS/OS and ELM integrity, may be to blame.^14,16,17,23

Figure 3. DME resolved after vitrectomy, but the IS/OS did not regenerate, suggesting a permanent loss of photoreceptor integrity.

We performed this study to test the hypothesis that postvitrectomy VA would improve when the following two requirements were met:

• preoperative integrity of the photoreceptors (confirmed by preservation of the IS/OS line); and

• resolution of DME (as confirmed by a decrease in CMT).

Previous studies have shown that an intact IS/OS line is a positive predictor of visual recovery after vitrectomy,^14,23 although Chhablani et al. reported that the preoperative integrity of the ELM may be a better predictor of postoperative visual improvement than is the IS/OS.¹⁷

We were unable to use the ELM as a predictor because we could detect it in only in a small number of patients in this study, and none of the patients had completely intact IS/OS lines. Our low IS/OS and ELM detection rates may have resulted from our use of color SD-OCT images and not gray scale representations, which may be superior at detecting IS/OS or ELM lines.^14,17

Alternatively, our results may have been due to the long duration of the DME and the effects of previous treatments, such as focal/grid laser photocoagulation and sub-Tenon’s injections of triamcinolone acetonide. Therefore, we categorized the eyes into an IS/OS(+) group if the IS/OS line was 30% or more intact and the remaining eyes into an IS/OS(-) group.

We discovered that eyes with integrity of the IS/OS line experienced a greater improvement in vision than those with minimal IS/OS integrity. We also noted that regeneration of the IS/OS line sometimes followed resolution of DME, possibly due to restoration of better alignment of photoreceptor cells.

Improved CMT generally, though incompletely, correlates with improved vision in several retinal vascular diseases. Our study showed visual improvement depended on both IS/OS integrity and macular thinning. However, the subset analyses showed these groups were small. We believe larger cohorts are needed to evaluate this correlation.

CMT decreased significantly by one month after vitrectomy with triamcinolone in the majority of IS/OS(+) eyes. Some of this early thinning may have been due to the effects of intraoperative triamcinolone.

CMT rebounded briefly at two months, possibly when the triamcinolone left the eye, before it decreased significantly again at four months and remained stable through the duration of the study. Several studies have shown that vitrectomy has a long-term ability to maintain a dry macula.^15,18

For some reason, macular thinning in the IS/OS(-) eyes was less robust than the IS/OS(+) eyes, as significant resolution of edema occurred in only seven of 20 IS/OS(-) eyes. Despite normalization of foveal contour and resolution of intraretinal cysts in these eyes, VA did not recover.

This outcome emphasizes the need for both preoperative IS/OS integrity and postoperative resolution of macular edema to effectuate long-term improvement of VA.

CONCLUSION

In conclusion, our study confirms the positive predictive value of preoperative IS/OS integrity and the need for postoperative resolution of macular edema for the improvement of VA after vitrectomy for DME.

We recommend that SD-OCT evaluation of the IS/OS and ELM lines be performed in larger prospective studies involving the use of vitrectomy and anti-VEGF drugs. Doing so may enable surgeons to identify eyes better that are likely to experience visual improvement before treatment is initiated.

Correlation of these findings with post-treatment clinical improvements should be evaluated in larger studies. RP

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