Comparison of automated vs manual analysis of corneal endothelial cell density and morphology in normal and corneal endothelial dystrophy-affected dogs.

OBJECTIVE: To determine the efficacy of automated imaging software of the Nidek ConfoScan 4 confocal biomicroscope at analyzing canine corneal endothelial cell density and morphology in health and disease, by comparing to a manual analysis method. ANIMAL STUDIED: Nineteen eyes of 10 dogs were evaluated and include three Beagles, three Jack Russell Terriers, and four miscellaneous breeds. Twelve clinically normal and seven eyes affected with corneal endothelial dystrophy (CED) were scanned and analyzed. PROCEDURES: Endothelial cell density (ECD), mean and standard deviation (SD) of cell area, percent polymegathism, mean and SD of the number of cell sides, and percent pleomorphism were calculated using automated and manual methods for each scan. RESULTS: The automated analysis showed significantly greater ECD in comparison with the manual frame method due to misidentification of cell domains in CED-affected dogs. No significant differences in ECD were observed between normal and CED-affected dogs in automated analysis, while CED-affected dogs showed significantly lower ECD in manual frame method and planimetry. Using both automated and manual methods, CED-affected dogs showed greater variability of cell area or the number of cell sides than normal dogs. CONCLUSION: The automated imaging software is unable to accurately identify cell borders in CED-affected dogs resulting in inaccurate estimates of ECD. Thus, manual analysis is recommended for use in clinical trials assessing adverse events associated with novel medical treatments and/or surgical procedures.

Comprehensive Clinical, Diagnostic, and Advanced Imaging Characterization of the Ocular Surface in Spontaneous Aqueous Deficient Dry Eye Disease in Dogs.

PURPOSE: To perform a comprehensive clinical, diagnostic, and imaging characterization of the ocular surface in West Highland White Terriers (WHWTs) diagnosed with aqueous deficient dry eye (ADDE) disease. METHODS: Six ADDE-affected and 13 ADDE-unaffected WHWT dogs were enrolled and underwent clinical assessment and disease scoring, tear osmolarity, phenol red thread test, Schirmer tear test, tear film breakup time, fluorescein staining, Rose bengal and lissamine green vital dye staining, meibometry, corneal esthesiometry, ultrasound pachymetry, optical coherence tomography, in vivo confocal microscopy, and conjunctival biopsy. Subjective assessment of their condition was provided by owner-reported surveys. RESULTS: ADDE-affected WHWT dogs had higher median clinical disease (conjunctiva: 5.75 vs. 0.00; cornea: 14.00 vs. 5.00; total: 17.50 vs. 5.00), vital staining (Rose bengal: 2.25 vs. 1.50; lissamine green: 2.00 vs. 1.00), and histologic disease (conjunctiva: 2 vs. 0) scores when compared with the controls. In addition, ADDE-affected WHWTs had significantly lower phenol red thread test (5.0 vs. 17.5, mm/15 s), Schirmer tear test (3 vs. 20, mm/min), tear film breakup time (3.6 vs. 13.9, s) values and higher area under the curve values for meibometry (394 vs. 245, meibometry units [MU]). There were no significant differences in other tear film tests performed. Advanced imaging revealed decreased tear meniscus height (optical coherence tomography) and variable pigment deposition within corneal epithelial cells (in vivo confocal microscopy). CONCLUSIONS: This comprehensive assessment of ADDE-affected WHWTs depicts the ocular surface changes associated with quantitative lacrimal gland dysfunction. Importantly, ADDE-affected WHWTs may prove a valuable naturally occurring ADDE model for investigating underlying pathophysiological mechanisms and the development of novel therapeutics.

In Vivo Imaging of Corneal Endothelial Dystrophy in Boston Terriers: A Spontaneous, Canine Model for Fuchs' Endothelial Corneal Dystrophy.

PURPOSE: Boston Terriers (BTs) have a greater prevalence of corneal endothelial dystrophy (CED), in comparison to other canine breeds. Similar to Fuchs' endothelial corneal dystrophy (FECD), this condition is characterized by endothelial cell degeneration with secondary corneal edema. This study assessed corneal morphology using in vivo confocal microscopy (IVCM) and Fourier-domain optical coherence tomography (FD-OCT) in BTs with and without CED. METHODS: The corneas of 16 BTs with CED and 15 unaffected, age-matched BTs underwent clinical evaluation and were imaged using IVCM and FD-OCT. A two-sample t-test or Mann-Whitney rank sum test were used to statistically compare parameters between groups. Data are presented as mean ± SD or median (range). RESULTS: Mean age did not significantly differ between affected and unaffected dogs at 10.0 ± 2.0 and 10.6 ± 2.4 years, respectively (P = 0.437). Females (69%) were overrepresented among the CED-affected dogs. In CED patients, IVCM demonstrated endothelial polymegathism and pleomorphism. Corneal endothelial density was significantly less (P < 0.001) in dogs with CED (1026 ± 260 cells/mm2) versus age-matched controls (2297 ± 372 cells/mm2). Fourier-domain OCT demonstrated a significant increase (P < 0.01) in central corneal and endothelium-Descemet's complex thickness in dogs with CED versus age-matched controls at 1019 (485-1550) or 536 (464-650) µm and 32 (22-56) or 25 (15-34) µm, respectively. CONCLUSIONS: Corneal endothelial dystrophy in BTs is a bilateral, adult-onset condition that shares many similarities with FECD. Thus, CED could serve as a spontaneous disease model to study the pathogenesis of and develop novel treatments for FECD.