Fig. 7.23 Late-phase fluorescein angiogram of the right eye of case 1 in September 2008. There is petalloid hyperfluorescence most prominent superior and temporal to the fovea although the epicenter of the thickening on the OCT false color map is inferonasal to the fovea

refractory DME can be larger than OCT measurement variability, which for an eye with macular thickness of 273 mm would be approximately 30 mm. The clinician may need to include this factor of short-term variability of macular thickness in refractory DME in clinical decision making to avoid restarting previously futile styles of treatment

and possibly inducing further side effects such as laser-induced paracentral scotomata or steroid-

induced pressure elevation without benefiting visual acuity.142,175

7.12 Case Report 2

A 77-year-old man with diabetes of 10 years duration and hypertension of 1-year duration was examined in 2000 and found to have DME reducing visual acuity in the left eye to 20/50. No OCT was available in our clinic in 2000, but clinically significant macular edema was found on stereoscopic slit-lamp biomicroscopy with a noncontact fundus lens and two sessions ofargon laser focal/grid photocoagulation were given on 16 March 2000 and 28 January 2002. The DME resolved both on clinical examination and by OCT measurements once that instrument became available to the practice. During follow-up, four consecutive normal CSMTs were recorded between 25 January 2005 and 21 August 2007 in consonance with the clinical examination that showed no macular thickening on stereoscopic slit-lamp biomicroscopy. The appearance of the fundus at this time is shown in

Fig. 7.25. At follow-up on 9 April 2008, the CSMT increased to 283 mm compared to the value of 205 mm on 21 August 2007 (Figs. 7.26 and 7.27). Clinically, the center of the macula was judged to be not thickened. The question arose whether the 78 mm increase in macular thickness represented a change in the macula in excess of the short-term fluctuation in macular thickness in an eye with regressed DME. In other words, was this recurrent DME and did it need to be treated?

The patient was observed without treatment and at follow-up on 11 November 2008 was noted to have spontaneous resolution of the macular thickening present at the previous examination. That is, as this case exemplifies, short-term fluctuation in CSMT in regressed DME is potentially larger than OCT measurement variability. For an eye with macular thickness of 205 mm, measurement

Fig. 7.25 Color fundus photograph documenting the appearance of the left eye of case 2 with regressed DME and a pattern of focal/grid laser scars

Fig. 7.26 Three OCT false color maps of the left eye of case report 2 documenting the regional pattern of macular thickness in a patient with regressed DME after two sessions of focal/grid photocoagulation given 7 years earlier. On 8 May

2008, there is OCT thickening that was not present at the 21 August 2007 visit. Without any therapy, there is spontaneous regression of this thickening as shown in the map from 11 November 2008

variability would be approximately 21 mm. The clinician may be advised to include the larger shortterm fluctuation factor for eyes with regressed DME in clinical decision-making.

Of the many OCT indices that can be followed in

the course of DME, the central subfield mean thickness (CSMT) is the best single measure.176,177 It is

more reproducible than center point thickness, yet is highly correlated (r ¼ 0.99) with the latter.176,177

Total macular volume (TMV) correlates somewhat less well with CSMT(r ¼ 0.76), but there have been no conclusions drawn from analyzing TMV that

would not have been drawn by studying CSMT instead.146,157 Other variables such as maximal thick-

ening of the inner zone and maximal thickening of

the grid have not added value to analyses using CSMT.157 OCT has also revealed the fact that serous retinal detachment is associated with DME in

9.7–26.0% of cases, a fact unappreciated in the ETDRS era.68,132,178–180 Serous retinal detachment

can be associated with mild or severe degrees of neural retinal thickening, with retinopathy featuring clustered microaneurysms or with few microaneurysms, and has little correlation with visual acuity impairment. It responds to treatments for DME, just as does the thickening of the neural retina, is not correlated with degree of capillary nonperfusion, and has little prognostic importance for outcome.116 Serous retinal detachment is not seen in the absence of some degree of neural retinal edema.180

8 a.m. Central Subfield Thickness (Microns)

Fig. 7.28 Reproduced with permission from Browning.176 Relative change in central subfield thickening from 8 a.m. to 4 p.m. by the 8 a.m. central subfield thickness in a study of

diurnal variation of macular thickness in eyes with diabetic macular edema. 181 When the baseline thickening is small, the scatter in the relative change in thickening becomes large

Optical coherence tomography was originally developed using time domain acquisition of images (TD-OCT).182 More recently, machines using spectral domain acquisition of images have been introduced (SD-OCT), and time domain machines, while prevalent in practice, are no longer being made. Spectral

domain technology allows faster acquisition of images and denser sampling of the macula.183–185

The normal values for SD-OCT and TD-OCT differ

because the segmentation algorithms define the retina layers differently.184,185 TD-OCT defines retinal

thickness as the distance between the internal limiting membrane and the photoreceptor inner segment/ outer segment boundary. SD-OCT defines retinal thickness as the distance between the internal limiting membrane and the retinal pigment epithelial layer. For this reason, retinal thickness values with SD-OCT are on average 50–60 mm thicker than

values with TD-OCT and are tightly correlated (r > 0.9).193–195 The axial resolution of SD-OCT is 2–7 mm compared to 10–15 mm with TD-OCT.184,186,187 This

leads to a more sensitive detection of cystoid changes in the macula with SD-OCT, such that prevalences of such morphologic findings must be qualified by describing the method of imaging in order to prevent potential confusion.141,188 Reproducibility is better with SD-OCT because of the greater number of scans obtained per unit of area of retina. For the central subfield, the mean coefficients of variation of TD-OCT and SD-OCT have been reported to be 1.33 and 0.53–0.66%, respectively.184,187

OCT is an excellent tool for objectively measuring macular thickening, but macular thickening is only modestly correlated with visual acuity (r = 0.52–0.53), which is the more important clinical variable.180,189 One potential explanation for the imperfect correlation is the effect of variable duration of edema, an elusive clinical variable to define.119 Diabetes also causes apoptosis of retinal neurons before edema develops, and causes dysfunction of the glial cells of the retina, reflected in abnormalities in the electroretinogram (ERG) and

thinning of the diabetic retina before edema develops.35 Other confounders that impair correlation of macular thickening and visual acuity include variations in macular capillary perfusion, RPE dysfunction and scarring, and media opacities. The importance of these effects in degrading visual acuity varies from case to case and for some effects varies in ways that are currently impossible to measure.35,68

Besides its usefulness in the detection of macular edema, OCT has value as a method of longitudinally following DME, a chronic disease that follows a course of years to decades, and is subject to multiple interventions over time.190 The important element in obtaining this function is the use of spreadsheet tabulation of the OCT with graphical capability (Fig. 7.29). A noncommercial program has been described using widely available spreadsheet software, and proprietary variations of this approach are appearing in electronic medical records products and the software that comes with OCT machines.190

OCT provides near histologic levels of detail in localizing edema within the retina and categorizing morphologic variations in edema. Specific cases can be seen in which cysts and edematous regions are present in any given layer of the retina, but in general

DME is characterized by thickening of the outer rather than the inner retina.68,132,178,191 Subretinal fluid has

been seen in 9.7–26.0% of eyes with DME and is not seen in the absence of neuroretinal edema.68,132,178–180

Various classifications of DME based on OCT morphology have been proposed. The most widely quoted classification proposes to grade DME into three OCT groups: sponge-like swelling, cystoid macular edema,

and subfoveal fluid; others combine these categories into hybrid subgroups.178,180 Because detection of

CME is machine dependent, the reproducibility of interclinician grading using this scale is unknown, and no consensus or standardization of OCT classifications of DME has been achieved, the proposed scales are considered to be provisional.

Fig. 7.29 Longitudinal plot of change in central subfield macular thickness (CSMT) in micrometers (top panel) and total macular volume (TMV) in mm3 (bottom panel) of a patient with diabetic macular edema followed over 29 months. The short arrow indicates argon laser focal/grid laser treatment. The long arrow indicates vitrectomy, internal limiting membrane peeling. The longitudinal display

allows easier recognition of signal (true changes in macular thickness) from noise (measurement variability, diurnal variation in macular thickness, and short-term variation in macular thickness). In addition, this format provides visualization of changes in OCT indices with interventions over time, a perspective difficult to achieve by flipping through sequential snapshot OCT images