Dear Editor,
We read with great interest the study by Sachan et al.1 examining the comparative efficacy of autologous platelet-rich plasma (aPRP) and conventional therapy for moderate-to-severe dry eye disease. The authors should be commended for implementing a robust design with clearly defined outcome measures and a meaningful follow-up period. While the therapeutic benefits of aPRP are compelling, we identified methodological and interpretive issues that affect the strength of clinical inferences, particularly regarding the evaluation of treatment response. Chief among these is the reliance on mean group differences in Ocular Surface Disease Index (OSDI) without reporting the proportion of patients achieving a minimal clinically important difference (MCID). Statistically significant differences in OSDI scores may not equate to symptom relief that is meaningful to patients. For instance, a 15-point OSDI reduction is commonly considered the MCID threshold.2 Reporting this would have contextualized the patient-perceived benefit and helped guide clinical adoption.
Similarly, while p values are frequently cited for intergroup comparisons of secondary outcomes such as tear break-up time, Schirmer’s test, and corneal fluorescein staining, these are time-varying, observer-dependent variables that can be influenced by environmental conditions.3 However, no stratified variance analysis or adjustment for within-subject correlation appears to have been performed, despite repeated measurements on the same eyes. In studies of bilateral ocular disease, paired-eye statistical models better account for intra-patient correlation than independent-sample t-tests,4 which were used in this study. The use of inappropriate models increases the risk of type I error, particularly with small sample sizes.
Additionally, the authors did not quantify the platelet concentration in the prepared aPRP drops. Given the direct link between platelet-derived growth factor content and epithelial recovery,5 the absence of dosage validation introduces uncertainty in replicability. This is clinically relevant because interindividual variability in baseline platelet levels can lead to inconsistent therapeutic effects, especially when generalizing across diverse patient populations.
Notably, the study concluded that aPRP improves visual acuity; however, the data revealed that best-corrected visual acuity (BCVA) changes were not statistically significant at any time point. Including BCVA as a primary outcome when it remained unchanged across groups risks overinterpretation, particularly when no prespecified thresholds were provided to define clinically meaningful change.
Finally, although conjunctival impression cytology data were a novel and welcome addition, the grading system used was not standardized or referenced, limiting the generalizability of the histopathologic interpretation. Without a validated scoring metric, reported cytological improvements should be interpreted with caution.
Despite these concerns, this study adds value to the ongoing exploration of biologics in ocular surface disease and reflects a growing interest in patient-specific regenerative therapies. Constructive scrutiny of methodology, particularly outcome reporting and statistical modeling, is essential for translating findings into clinical practice. We appreciate the authors’ contributions to this evolving field.
