**Purpose.**:
To determine whether the volume of retinal tissue passing between the inner and outer retina in macular edema could be used as an indicator of visual acuity.

**Methods.**:
Diabetic and uveitic patients with cystoid macular edema (81 subjects, 129 eyes) were recruited. Best corrected logMAR visual acuity and spectral optical coherence tomography (OCT/SLO; OTI, Toronto, ONT, Canada) were performed in all patients. Coronal OCT scans obtained from a cross section of the retina between the plexiform layers were analyzed with a grid of five concentric radii (500, 1000, 1500, 2000, and 2500 μm centered on the fovea). The images were analyzed to determine the amount of retinal tissue present within each ring. A linear regression model was developed to determine the relationship between tissue integrity and logMAR visual acuity.

**Results.**:
A linear relationship between tissue integrity and VA was demonstrated. The volume of retinal tissue between the plexiform layers in rings 1 and 2 (up to 1000 μm from the foveal center) predicted 80% of visual acuity. By contrast, central macular thickness within the central 1000 μm predicted only 14% of visual acuity.

**Conclusions.**:
This study showed that the cross-sectional area of retinal tissue between the plexiform layers in cystoid macular edema, as imaged by OCT, is the best indicator of visual function at baseline. Further prospective treatment trials are needed to investigate this parameter as a predictor of visual outcome after intervention.

^{ 1 –5 }

^{ 5 }

^{ 6 –9 }with further studies claiming the beneficial effects of treatments designed to reduce CME.

^{ 10 –15 }

*z*-plane of the retina. However, scanning electron microscopy shows that more commonly a single cystic space is present within which a number of structures extend from the inner to the outer retina. Such structures consist of columns of Müller's fibers together with the axonal elements of bipolar cells passing between the two plexiform layers.

^{ 16 –18 }Empiric studies have demonstrated that the two plexiform layers together with the outer limiting membrane form a physical resistance barrier to fluid movements.

^{ 19 }Thus, extracellular fluid may be contained within layers defined by these resistance barriers. In diabetic retinopathy, cystic spaces may occur either between the inner and the outer plexiform layers or between the outer limiting membrane and the outer plexiform layer. In the former location, there is a potential to displace bipolar cells leading to cell loss or compromised function, while in the latter, only photoreceptor cells are at risk.

^{ 20,21 }

^{ 16–17 }

^{ 22 }Thus, an optimal measurement of potential function would be an evaluation of the number of vertical elements passing between the plexiform layers, their diameter, and their eccentricity from the fovea.

*x–y*plane (B-scan), such as single line, radial, and raster scans, could be obtained, as well as coronal images within the

*z*plane (C-scan).

^{ 23 }

*x*-axis of the coronal image.

^{ 24 }The second part of the program counted the number of white pixels present within each ring, thus giving a measure proportionate to the potential number of connections passing between the two plexiform layers. The number of pixels of spared tissue within each annulus was converted to an area in square millimeters by scaling the ratio of the number of pixels of spared tissue to the total number of pixels in the annulus by the area in square millimeters of the annulus.

*P*< 0.05 indicated a significant difference from normal), correlation coefficients were calculated to evaluate the association between VA and the other six outcome measures.

*P*= 0.05 and 0.10 for removal. Stepwise linear regression is an extension of simple linear regression where the dependent variable is predicted by a linear equation involving one outcome or independent variable and a constant. In stepwise linear regression, multiple variables can be linearly combined in the model. They are entered automatically by the statistics software provided they make a statistically significant improvement in the model. Stepwise linear regression has been used in a large number of areas.

^{ 25 }

^{ 26 }

*P*= 0.000–0.200); therefore, Spearman rank correlation coefficients were calculated. Their values, together with the associated statistical significance and the

*R*

^{2}values are given in Table 2. Figure 6 illustrates the

*R*

^{2}values reported as percentages of variation in VA explained by the outcome measures (CMT or the tissue sparing within each of the five rings).

Variable | r _{s} | P (Two-Tailed) | R 2 (%) |
---|---|---|---|

CMT | +0.407 | <0.001 | 16.6 |

Tissue spared in ring 1 (500 μm) | −0.832 | <0.001 | 69.2 |

Tissue spared in ring 2 (1000 μm) | −0.841 | <0.001 | 70.7 |

Tissue spared in ring 3 (1500 μm) | −0.624 | <0.001 | 38.9 |

Tissue spared in ring 4 (2000 μm) | −0.277 | 0.001 | 7.7 |

Tissue spared in ring 5 (2500 μm) | −0.134 | 0.130 | 1.8 |

*CMT*is the central macular thickness (millimeters), and

*T*

_{1}and

*T*

_{2}are the areas of tissue sparing in square millimeters in rings 1 and 2, respectively. This model had an

*R*

^{2}value of 80.7%, indicating that equation 1 accounted for more than 80% of the variation in logMAR VA. It is noteworthy that the most predictive variable was

*T*

_{2}, and this alone could predict 74.4% of the variation in logMAR VA in a linear model. The significance of this result will be commented on further in the Discussion section.

^{ 22 }foveal cones may connect to bipolar cells displaced 500 μm radially from the inner and outer segments. Thus, this lateral displacement of connections between foveal cones and ganglion cells explains the dependency of VA on the tissue integrity in both rings 1 and 2.

^{ 22 }and a pathologic study measuring laser damage to foveal photoreceptor cells.

^{ 27 }Sjöstrand et al. measured the radial offset produced by cone fibers within the layer of Henle and demonstrated that, at the foveal border (0.5–0.8 mm or 1.8–2.9° eccentricity), the mean offset due to the fibers of Henle and the mean total lateral displacement were at a maximum of 0.32 ± 0.03 and 0.37 ± 0.03 mm, respectively, thereafter steeply decreasing outside the foveal border to an eccentricity of 2 to 2.5 mm. This anatomic finding confirms that structural damage involving the neural retina up to 1 mm from the foveal center may have implications for loss of information generated within the fovea.

^{ 28 }Given that the approximate diameter of bipolar axons is 0.5 μm and the diameter of Müller fibers is between 5 and 10 μm, we can estimate that, in normal conditions for each Müller fiber, there are approximately 34 to 68 adjacent bipolar neurons around their circumference.

^{ 29 }changes to their environment maybe of particular importance.

*R*

^{2}values ranging from 0.08 to 0.54)

^{ 9 }compared with the results presented in the current paper.

^{ 30 –32 }The apparent correlation between the increase in retinal thickness and the decrease in VA may be explained by the results of the present paper whereby increase in thickness will be associated with increase in loss in viable axons. The more direct approach to assessing neuronal survival in the present study would also explain why the correlation values are so much better.