A Response to: Letter to the Editor Regarding "Agreement Between Trend-Based and Qualitative Analysis of the Retinal Nerve Fiber Layer Thickness for Glaucoma Progression on Spectral-Domain Optical Coherence Tomography".

We thank Hwang et al. for their thoughtful letter in response to our recently published article [1], and we agree with their astute observation that peripapillary retinal nerve fiber layer (RNFL) retinoschisis further contributed to a false appearance of progression in our case example presented in Fig. 2. Several prior studies have described the co-prevalence of peripapillary RNFL retinoschisis in eyes with glaucoma [2-5], which may impact approximately 6% of glaucoma patients according to two recent cohort studies [3, 4]. In both of these studies, peripapillary RNFL retinoschisis was significantly more likely to be present in glaucomatous compared to healthy eyes [3, 4]. Van der Schoot et al. detected focal peripapillary RNFL retinoschisis in 7 of 117 glaucomatous eyes and 0 of 91 healthy control eyes [4]. Similarly, in the Investigating Glaucoma Progression Study, Lee and colleagues reported that peripapillary RNFL retinoschisis was present in 5.9% of glaucoma cases compared to only 0.5% of healthy controls. Of note, in a multivariate model, higher intraocular pressure at the time of spectral domain-optical coherence tomography (SD-OCT) scan was also significantly associated with the presence of peripapillary retinoschisis (odds ratio = 1.48, p = 0.001).

Several groups have observed that peripapillary RNFL retinoschisis is often topographically correlated with an RNFL defect, and can thus impact correct interpretation of the true RNFL thickness [2-5], as it did in our case example. Thus, care should be taken not to overestimate the RNFL thickness whenever such retinoschisis is noted on review of the SD-OCT imaging. Moreover, such peripapillary retinoschisis is typically a transient phenomenon [2-5]. Fortunately, peripapillary RNFL retinoschisis only rarely extends into the macula [5], and tends to spontaneously resolve without any impact on visual function or evidence of glaucomatous progression [2-5]. Thus, when reviewing serial SD-OCT in patients with glaucoma, it is critical to neither overestimate the RNFL thickness in eyes with retinoschisis, nor erroneously attribute the resolution of such retinoschisis to glaucomatous progression.