A Comparative Study of Efficacy and Acceptability of a new Paradigm Foldscopy and Conventional Microscopy for analysis of Goblet Cells in patients with Limbal Stem Cell Deficiency

Abstract Background Assessment of conjunctival goblet cells by impression cytology is an established diagnostic approach for evaluating ocular surface disorders, particularly limbal stem cell deficiency (LSCD), dry eye disease (DED), and Stevens-Johnson syndrome (SJS). Conventional light microscopy remains the gold standard; however, its use is limited in resource-constrained settings because of high equipment costs and the requirement for trained personnel. Foldscope, an inexpensive origami-based paper microscope, has emerged as a promising point-of-care diagnostic device. Purpose To evaluate the efficacy and acceptability of Foldscope compared with conventional bright field microscopy for the assessment of conjunctival goblet cells in patients with ocular surface disorders. Methods Fourteen patients (28 eyes) diagnosed with ocular surface disease were prospectively enrolled. Conjunctival impression cytology specimens were collected and stained with haematoxylin and eosin (H&E). Slides were independently evaluated using Foldscope and a high-resolution Zeiss automated virtual bright field microscope (automated Digital virtual Slide Imaging System). Goblet cell density, epithelial morphology, and cytological alterations were graded according to Nelson's grading system. Results Among the 14 patients (28 eyes), four were diagnosed with Stevens–Johnson syndrome, while the remaining had dry eye disease. Females predominated (10/14). Reduced goblet cell density was observed in four eyes, while complete goblet cell loss was detected in eight eyes. Goblet cell density demonstrated an inverse association with disease severity. Foldscope successfully identified epithelial morphology and goblet cells in most specimens, although image quality and field of view were inferior to conventional microscopy. Conclusions Foldscope demonstrates considerable potential as a portable, low-cost screening tool for conjunctival goblet cell assessment in ocular surface diseases. Although it cannot currently replace conventional microscopy for definitive diagnosis or disease grading, it may provide a valuable alternative in low-resource settings. Strengths First comparative evaluation of Foldscope for conjunctival impression cytology. Direct comparison with a Zeiss automated virtual microscope. Assessment of clinically relevant ocular surface disorders (DED, LSCD, and SJS). Demonstrates the potential of an affordable, portable imaging platform for point-of-care ophthalmic diagnostics.