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I would like to thank Drs Brown and Bradley for their queries in relation to our recently published article. 1 Kojima T. Ishida R. Dogru M. et al. The effect of autologous serum eye drops in the treatment of severe dry eye disease a prospective randomized case-control study. Am J Ophthalmol. 2005; 139: 242-246 Abstract Full Text Full Text PDF PubMed Scopus (197) Google Scholar First, I would like to note that any double masked prospective trial involving autologous serum eye drops is not practical and very difficult in a clinical setting. Even if you use special bottles or containers, the patients may communicate with each other while waiting for an ophthalmic examination and can recognize from the color of the eye drops whether they are using serum (yellow) or nonpreserved artificial tears (clear). In our study, the patients were advised to strictly conform to the protocol of the study, not to switch their drops, or change the frequency of instillations during the study period. The control patients were also provided with extra bottles to prevent such occurrence. Decreased compliance occurs more frequently with longer term trials; we believe that the interval chosen for our study was appropriate in terms of compliance as well. The patients were specifically questioned on these compliance issues on their next visit and there were no “poor compliance subjects” in this study. Otherwise, they would be excluded from the trial. Although we totally agree with the validity of OSDI in measuring patient symptoms, 2 Schiffman R.M. Christianson M.D. Jacobsen G. et al. Reliability and validity of the Ocular Surface Disease Index. Arch Ophthalmol. 2000; 118: 615-621 Crossref PubMed Scopus (1756) Google Scholar there is still no international consensus on which symptom questionnaire to use in prospective dry eye trials, and we based our decision to use visual analog scales on previously published dry eye work assessing symptoms. 3 Nichols K.K. Begley C.G. Caffery B. et al. Symptoms of ocular irritation in patients diagnosed with dry eye. Optom Vis Sci. 1999; 76 (:838–844): 12 Crossref PubMed Scopus (48) Google Scholar , 4 Malet F. Karsenti D. Pouliquen P. Preservative-free ocular hydrating agents in symptomatic contact lens wearers saline versus PVP solution. Eye Contact Lens. 2003; 29 (:38–43): 1 Crossref Google Scholar Please also note that we used Soft Santear (Santen Pharmaceutical, Osaka, Japan) eye drops which contained 0.1% and 0.4% sodium chloride and potassium chloride, respectively, without preservatives. This is a widely available eye drop for the clinical use in Japan. This product can undergo freeze and thaw process without a change in viscosity. We thank the authors again for bringing up these essential points. The Effect of Autologous Serum Eye Drops in the Treatment of Severe Dry Eye Disease: A Prospective Randomized Case-Control StudyAmerican Journal of OphthalmologyVol. 140Issue 3PreviewIn the article by Kojima and associates,1 the authors discuss the use of autologous serum (AS) eye drops for the treatment of severe dry eye. These authors have published many important basic and clinical articles regarding AS, which we follow with enthusiasm. However, we would like to point out several relatively serious design flaws in the current experiment so that they may be rectified in future studies. Full-Text PDF