Specular microscopy: A practical guide for the assessment of corneal endothelial health and device selection

(Image Credit: AdobeStock/studiomay)

Reviewed by Ivo Guber, MD, FMH, FEBO, FICO

Specular microscopy is a valuable in-clinic tool for patients with corneal endothelial disease or who are undergoing corneal examination before other surgeries. Research data published earlier this year could help clinicians gain a better understanding of what to look for in a specular microscope, and how to interpret inter- and intradevice repeatability results in a way that benefits their existing practice framework.

Ivo Guber, MD, FMH, FEBO, FICO, is a consultant ophthalmic surgeon at the University of Geneva, Switzerland. He is also the owner and medical director at Augenchirurgie.ch in Winterthur, Switzerland. Guber and colleagues published an article earlier this year in Medicina (Kaunas),¹ which provided real-life evidence of interdevice variances in specular microscopy. These data were also the subject of a prior lecture² by Guber, first presented at the South African Society of Cataract and Refractive Surgery International Congress in 2022.

Importance of the specular microscope

The investigators’ findings brought attention to 2 specular microscopy measurements, corneal endothelial cell density (ECD) and central corneal thickness (CCT). Before choosing a specular microscope for their practice, a clinician should investigate the accuracy of the data produced by the machine. Reliable and reproducible data are paramount, and because each device is unique, practitioners should research to assess whether the types of data rendered by a device will fit their clinical needs. Compatibility and comparability with preexisting devices in the clinic are also important.

Guber also encouraged clinicians to consider whether they have specific handling needs. Easy-to-use controls and quickly legible displays are important and may require more serious consideration if the physician plans to delegate tasks to trainees, nurses or other staff.

When clinicians are choosing a specular microscope, the financial aspects of the decision deserve particular attention. The 4 devices showcased in Guber’s presentation ranged from approximately €19,800 to €29,100 ($20,918 to $30,745), and he highlighted that the upfront price and amortization period could both be detrimental to smaller clinics. Guber used his clinic as an example: Based on the price of the specular microscope used, it took approximately 1 year, or 283 individual specular microscopy measurements, to offset the cost of the machine.² A practitioner should assess whether these investments will adequately serve the needs of a clinic’s patient base.

Two devices: Nidek CEM-530 and Tomey EM-4000

Study investigators assessed 2 commercially available specular microscopes, the CEM-530 (Nidek, Japan) and the EM-4000 (Tomey, Germany), in a real-life clinical setting. These 2 devices are comparable in price: Guber reported the Tomey EM-4000 was priced at €19,800 ($20,918) and the Nidek CEM-530 cost €20,800 ($21,976).² Both devices perform noncontact specular microscopy and have integrated noncontact pachymetry. The Nidek device has a manual alignment; endothelial measurement is self-triggered.

In the study, patients presented for ophthalmic examination before planned cataract surgery. Investigators included 112 eyes of 56 patients (mean age, 61.05 years [range, 22-85]; 24 female, 32 male). Each eye was measured 3 times with each device, and staff recorded ECD and CCT values for each measurement (Figure 1).

Figure 1. Intradevice cell density and central corneal thickness comparisons

Figure 2. Interdevice comparisons of the Nidek CEM-530 and Tomey EM-4000. (All data¹ courtesy of Kecik M, Kropp M, Thumann G, Pajic B, Guber J, Guber I.)

Masked researchers, not linked to the clinic, statistically analyzed the results using a Friedman test, analysis of variance, a Wilcoxon signed-rank test, a Mann-Whitney test, and a paired t-test, according to sample distribution determined by a D’Agostino-Pearson normality test.

Intradevice repeatability values

According to the authors, both specular microscopes had consistent intradevice results. Guber and colleagues wrote, “Tomey EM-4000 measured an ECD of 2390 ± 49.57 cells/mm² (range 799-3010 cells/mm²) and a CCT of 546 ± 5.104 μm (range 425-615 μm), while the Nidek CEM-530 measured an ECD of 2417 ± 0.09 cells/mm² (range 505-3461 cells/mm²) and a mean CCT of 546.3 ± 4.937 μm (range 431-621 μm).” The intradevice measurements were statistically significant in accordance for each eye (Tomey, OD vs OG, P = .0796; Nidek, OD vs OG, P = .9910; Tomey measurement: 1-3, P = .7972; Nidek measurement: 1-3, P = .6207).

Interdevice differences and theories

The ECD values registered on the Nidek device were slightly higher than those registered on the Tomey device (Figure 2); the CCT (values also had some interdevice discrepancies. “Interdevice variability in terms of endothelial cell count and central corneal thickness showed a reduced endothelial cell count with the Tomey compared to the Nidek device with an average of 121.2 cells (4.87%) less (* P = .0175),” the authors wrote.² “Measured central corneal thickness was lower in the Tomey with a difference of 16.75 μm (3.07%) (* P = .0125).”

Guber and colleagues theorized that a number of factors could account for the Nidek’s higher ECD values throughout the study. The difference could be accounted for by a slightly larger endothelial capture field. The photographic range on the Tomey specular microscope is 0.25 mm by 0.54 mm, and the range on the Nidek is 0.25 mm by 0.55 mm.

“As the average diameter of a human corneal endothelial cell is 20 μm or 0.02 mm, [the Nidek device] is able to include more cells in the photograph for analysis," the investigators wrote.

The devices may also use different methods to calculate cells at the edge of
the imaging frame, and automated algorithms may include or exclude “edge” cells differently between devices.

Additionally, the capture field of a specular microscope is small in comparison to the total corneal endothelium. Specular microscopes may have automatic centering, but when taking repeated measurements, the photograph will not be microscopically aligned with previous images. Cell density variations drive a need for repeated imaging of both central and peripheral corneal zones: It is recommended that clinicians image at least 20% of the endothelial cell surface, which commercially available specular microscopy devices can only achieve with repeated imaging.

“The difference between both devices is relatively small (4.87%), and an argument can be made that this bears little clinical significance,” the study’s authors emphasized.

Conclusion

Both specular microscopes provided reliable ECD and CCT measurements in a clinical setting, and Guber described the intradevice repeatability for both machines as “excellent.” However, the interdevice variability was statistically significant, and the Nidek device provided higher values for the ECD count in the cases presented. The interdevice comparability is clinically acceptable. Guber advised physicians to take note when comparing results between devices, especially in larger clinics or hospital centers, or in multicenter studies about corneal endothelial tissues.

Ivo Guber, MD, FMH, FEBO, FICO

E: ivo.guber@augenchirurgie.ch

Guber is a specialist in cornea, cataract, and refractive surgery and the leading eye surgeon at Augenchirurgie.ch eye centers in Switzerland. He is also a senior consultant at the University Hospital of Geneva, Switzerland.

References

1. Kecik M, Kropp M, Thumann G, Pajic B, Guber J, Guber I. Intradevice repeatability and interdevice comparison of two specular microscopy devices in a real-life setting: Tomey EM-4000 and Nidek CEM-530. Medicina (Kaunas). 2024;60(7):1110. doi:10.3390/medicina60071110

2. Guber I. Finding the best specular microscope for your clinic. Presented at: South African Society of Cataract and Refractive Surgery International Congress; November 3-5, 2022; Cape Town, South Africa.