Response to the Letter to the Editor Submitted by Dr. JoAnn C. L. Schuh

Dear Dr. Elmore,

Thank you for the opportunity to respond to the Letter to the Editor submitted by Dr. Schuh.

In her Letter to the Editor, Dr. Schuh indicates that lymphoid aggregates and nodules in the conjunctiva (figures 2 and 3 of our paper entitled “Spontaneous Findings in the Eyes of Cynomolgus Monkeys (M. fascicularis) of Mauritian Origin”) without any other sign of inflammation do not represent a lymphocytic or mononuclear-cell infiltrate or an inflammatory response but are representations of the mucosa-associated, in this case conjunctiva-associated, lymphoid tissue (MALT or CALT). The authors agree with Dr. Schuh that the findings described in figures 2 and 3 are consistent with CALT, which should have been addressed and discussed in the manuscript. Furthermore, the findings should not have been summarized under “inflammatory lesions.” However, it should be noted that the descriptions in the Result section (pp. 275–76) for figures 1–3 (and also in legends) clearly mention that there were no features of inflammation. Although the chosen nomenclature (figure 2: accumulation of mononuclear cells, figure 3: lymphoid nodule) is descriptive and not in conflict with a CALT structure, we agree that they should not be confused with an inflammatory change.

We wish to bring to your attention that the morphologic attributes of conjunctiva vary in different parts of this tissue. Histology of palpebral conjunctiva is significantly different from bulbar conjunctiva (Klintworth and Cummings 2012). Eyeball specimens in our study were processed as per routine toxicologic pathology workup (tissues of interest were collected per Standard Operating Procedures of laboratories I and II), wherein the eyeballs were processed and examined with only bulbar conjunctiva in the globe. Note that upper or lower palpebral (marginal/tarsal/orbital) conjunctiva were not part of tissue sampling. To date, including references quoted by Dr. Schuh, investigators have recognized and described MALT or MALT-like structures primarily of the palpebral conjunctiva. Systematic evaluation of lymphoid tissues within the conjunctiva has shown that in both human and rabbit (Cain and Phillips 2008; Knop and Knop 2000), the highest concentration of CALT is in the palpebral conjunctiva, with many fewer lymphoid follicles in fornical or bulbar regions. Moreover, the CALT is still being described and investigated to define the histophysiological similarities to bronchus-associated lymphoid tissue or Peyer’s patches in multiple laboratory animals, including nonhuman primates (Steven and Gebert 2009).

In conclusion, we acknowledge that the structures shown in figures 2 and 3 are morphologically consistent with CALT; secondly, these structures should not have been reported under “inflammatory changes.” Although we believe that the chosen descriptive terminology “accumulation of mononuclear cells” and “lymphoid nodule” are adequate, these findings are better defined as CALT.

Submitted by

Jochen Woicke Bristol-Myers Squibb, Mount Vernon, Indiana, USA Solomon Haile Charles River Laboratories, Senneville, Quebec, Canada Jagannatha Mysore Bristol-Myers Squibb, New Brunswick, New Jersey, USA Michael Peden Bristol-Myers Squibb, Mount Vernon, Indiana, USA Typhaine Lejeune Charles River Laboratories, Senneville, Quebec, Canada Thomas P. Sanderson Bristol-Myers Squibb, Mount Vernon, Indiana, USA Thomas Brodie Bristol-Myers Squibb, New Brunswick, New Jersey, USA