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Background: Ophthalmic viscosurgical devices (OVDs) are commonly used during cataract surgery to protect the corneal endothelium. A systematic literature review and meta-analysis were conducted to assess the clinical evidence of OVDs composed of chondroitin sulfate-hyaluronic acid (CS-HA) versus other OVDs in maintaining endothelial cell density (ECD) and corneal thickness (CT). Methods: MEDLINE and EMBASE databases were searched from 2000 to 2020. Randomized controlled trials (RCTs, N ≥ 20 per group) comparing an OVD containing CS-HA (ie, VISCOAT®, DuoVisc® or DisCoVisc®) to any other OVD were included. The identified comparators were limited to the OVDs found in the literature, which included those composed of HA-only or hydroxypropyl methylcellulose (HPMC). Outcomes of focus included changes in ECD (baseline to 3 months) and CT (baseline to 24 hours). Meta-analyses were performed using R software, to assess mean differences (MD) in ECD and CT change between CS-HA OVDs and HA-only or HPMC OVDs. Results: A total of 966 abstracts were screened, and data were extracted from 12 RCTs. Meta-analyses using a random-effects model revealed significantly lower percent (%) decrease in ECD for CS-HA OVDs compared to both HA-only (MD: −4.10%; 95% CI: −5.81 to −2.40; p < 0.0001; 9 studies) and HPMC (MD: −6.47%; 95% CI: −10.41 to −2.52; p = 0.001; 2 studies) products. Similarly, % CT increase was significantly lower with CS-HA than with HA-only OVDs (MD: −3.22%; 95% CI: −6.24% to −0.20%; p = 0.04; 4 studies). However, there were no significant differences when comparing % CT change between CS-HA and HPMC OVDs (MD: 2.65%; 95% CI: −0.43% to 0.95%; p = 0.4; 2 studies). Conclusion: CS-HA OVDs lead to less postoperative loss of endothelial cells and may better protect corneal endothelium during cataract surgery, relative to other OVDs. Future randomized studies may be needed to solidify these findings.

Introduction: During our clinical practice and research, we encountered an interchangeability problem when using the SP-2000P and SP-3000P TopCon corneal specular microscopes (CSMs) (TopCon Medical Systems, Tokyo, Japan) regarding the endothelial cell count (ECC). We describe a method to improve interchangeability between these CSMs. Methods: Five consecutive good-quality endothelial cell photographs were obtained in 22 eyes of 11 subjects. An ECC comparison between the two CSMs was performed after (I) gauging and calibration by the manufacturer, (II) adjustment of the magnification, (III) correction after external horizontal and vertical calibration. Results: There was a statistically significant difference between the ECC of the SP-2000P and SP-3000P at the start. The SP-2000P counted an average of 500 cells/mm2 more than the SP-3000P (p=0.00). After correction for magnification and determining a correction factor based on external calibration, the difference between the ECC of the SP-2000P and the SP-3000P was then found to be 0.4 cells/mm2 and was not statistically significant (p=0.98). Discussion: We propose a method for improving interchangeability, which involves checking magnification settings, re-checking magnification calibration with external calibration devices, and then calculating correction factors. This method can be applied to various specular or confocal microscopes and their associated endothelial cell analysis software packages to be able to keep performing precise endothelial cell counts and to enable comparison of ECCs when a CSM needs to be replaced or when results from different microscopes need to be compared.

ObjectiveTo 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 studiedNineteen 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.ProceduresEndothelial 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.ResultsThe 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.ConclusionThe 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.

Purpose: To analyze the influence of low endothelial cell density (ECD) of donor cornea tissue, donor age, and sex on the transplant survival rate after Descemet stripping automated endothelial keratoplasty (DSAEK). Methods: Graft ECD, age, and sex of donors used for DSAEK (n = 1789) during 7 years (2007-2014) in 4 Scandinavian hospitals were assessed for potential association with transplant survival at 2 years of follow-up using a Cox regression model correcting for confounding factors. The data were obtained from The Swedish Cornea Transplant Registry. Results: Transplant failure occurred in 196 patients, with 69 early failures during the first 3 postoperative months, and 127 late secondary failures. Twenty-five of the late secondary failures were due to rejection. Reversible rejections occurred in 67 patients. There was no significant impact of donor age [hazard ratio (HR) 1.0, 95% confidence interval (CI), 0.99-1.02, P = 0.32] or endothelial cell count (HR 1.00, 95% CI, 0.99-1.01, P = 0.3) on the survival rate of DSAEK transplants at 2 years of follow-up. The use of donor grafts with low ECD (, 2300 cells/mm(2)) did not influence the survival rate (HR 1.3, 95% CI, 0.76-2.35, P = 0.31). Male donor sex was associated with lower 2-year graft survival (HR 1.5, 95% CI, 1.042.28, P = 0.03), but not with rejection events (P = 0.26). Conclusions: Based on data from The Swedish Cornea Transplant Registry, low donor ECD was not detrimental to graft survival, whereas donor sex seemed to influence the outcome at the end of the 2-year follow-up.

PURPOSE: To perform a longitudinal evaluation of subjects who had undergone penetrating keratoplasty, using slit scanning confocal microscopy. METHODS: In vivo confocal microscopy was used to evaluate the central cornea of four subjects who had recently undergone penetrating keratoplasty. Subjects were examined on four occasions over a 12-month period after surgery. Quantitative and qualitative aspects of corneal morphology were compared against data from normal control subjects. RESULTS: The epithelium varied in appearance between subjects and took at least 12 months to return to a similar arrangement to that seen in normal eyes. Bowman's layer was viewed as an acellular layer immediately after surgery with no evidence of nerve fibres, although nerve components were apparent 12 months after surgery. Stromal nerves were not visible immediately after surgery. One year following penetrating keratoplasty there was evidence of thin nerves running a straight course through the central stroma. Keratocyte density in the anterior and posterior stroma was lower in the transplanted cornea but appeared to remain constant over a period of 1 year. Activated keratocytes were seen in the anterior stroma of all subjects; they appeared to be responsible for significant levels of corneal haze. The time period within which this keratocyte activation occurred varied between individuals. Endothelial cell density decreased at an accelerated rate over the 12-month period. CONCLUSIONS: Confocal microscopy allows cellular changes to be monitored in vivo following penetrating keratoplasty and may assist clinicians in understanding postoperative recovery.

PURPOSE: To investigate whether benoxinate hydrochloride 0.4% used to make confocal microscopy more comfortable alters the morphology of the cornea as viewed with the confocal microscope. METHODS: Confocal microscopy was performed on both eyes of 10 subjects prior to instillation of either topical anaesthetic or non-preserved sterile saline, on two randomly ordered occasions. Images of all corneal layers were analysed quantitatively and qualitatively in a masked fashion. RESULTS: The images were similar in appearance in 5/10 subjects, there was greater clarity when anaesthetic was instilled in 4/10 subjects, and in the remaining subject there was greater clarity when saline was used. Anaesthetic had no influence on anterior keratocyte density (AKD), posterior keratocyte density (PKD) or endothelial cell density (ECD). CONCLUSIONS: Local anaesthetic does not affect corneal morphology as imaged using the confocal microscope. However, failure to use anaesthetic may lead to a degradation of image quality due to patient discomfort and excessive eye movements.

PURPOSE: To document qualitative and quantitative changes in the normal, healthy human cornea with age using the confocal microscope. METHODS: The central corneas of 120 subjects (mean age, 41 years; range, 11 to 80 years) were examined using an in vivo slit-scanning real-time confocal microscope. Images of the corneal stroma and endothelium from both eyes of each subject were semiautomatically analyzed in an observer-masked, randomized manner. RESULTS: Anterior keratocyte density, posterior keratocyte density, and endothelial cell density were shown to be unaffected by the sex of the subject with p values of 0.46, 0.55, 0.50, respectively (multivariate analysis of variance). No statistically significant difference was detected between right and left eyes for all corneal layers examined. The anterior keratocyte density, posterior keratocyte density, and endothelial cell density decreased at a rate of 0.48, 0.22, and 0.33% per year, respectively. A positive correlation was found between the coefficient of cell variation and age. CONCLUSIONS: This data constitutes essential normative data that can be used as a control in further research into abnormal corneal conditions.