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Figure.
Bland-Altman Analyses
Bland-Altman Analyses

Bland-Altman analyses of agreement between intrasession measurements (images 1A and 1B) (A), between intersession measurements (images 2 and 3) (B), and between fixating vs nonfixating eye measurements (C). ECD indicates endothelial cell density; solid line, mean difference; and dotted lines, ±1.96 SDs from the mean (95% limits of agreement).

Table.  
Mean ECD and Session Agreement for the Different Sessions in Both Parts of the Study
Mean ECD and Session Agreement for the Different Sessions in Both Parts of the Study
1.
Sherrard  ES, Novakovic  P, Speedwell  L.  Age-related changes of the corneal endothelium and stroma as seen in vivo by specular microscopy. Eye (Lond). 1987;1(pt 2):197-203.PubMedArticle
2.
Bahn  CF, Glassman  RM, MacCallum  DK,  et al.  Postnatal development of corneal endothelium. Invest Ophthalmol Vis Sci. 1986;27(1):44-51.PubMed
3.
Kaufman  HE, Capella  JA, Robbins  JE.  The human corneal endothelium. Am J Ophthalmol. 1966;61(5, pt 1):835-841.PubMedArticle
4.
Speedwell  L, Novakovic  P, Sherrard  ES, Taylor  DS.  The infant corneal endothelium. Arch Ophthalmol. 1988;106(6):771-775.PubMedArticle
5.
Benetz  BA, Gal  RL, Ruedy  KJ,  et al; Cornea Donor Study Group.  Specular microscopy ancillary study methods for donor endothelial cell density determination of Cornea Donor Study images. Curr Eye Res. 2006;31(4):319-327.PubMedArticle
6.
de Sanctis  U, Machetta  F, Razzano  L, Dalmasso  P, Grignolo  FM.  Corneal endothelium evaluation with 2 noncontact specular microscopes and their semiautomated methods of analysis. Cornea. 2006;25(5):501-506.PubMedArticle
Research Letter
December 2015

Validation of Corneal Endothelial Specular Microscopy in Children Under General Anesthesia

Author Affiliations
  • 1Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
JAMA Ophthalmol. 2015;133(12):1474-1476. doi:10.1001/jamaophthalmol.2015.3695

Our current knowledge of the corneal endothelium in early childhood including its development and response to disease and surgery is suboptimal,13 largely owing to the technical difficulties involved in obtaining specular microscopy (SM) images in very young patients. The gold-standard technique for SM is to acquire images with central fixation while the patient is alert and upright, enabling images of the same corneal region each time. We have modified this technique to capture SM images in children under general anesthesia (GA) who are positioned in the lateral decubitus position with centration of the eye in the display reticle. However, because the patient is not able to fixate on a target, it is not clear whether this acquisition technique is reproducible.

Methods

Children with normal anterior segments undergoing GA for various ophthalmic indications were recruited prospectively. Endothelial images were taken using a noncontact specular microscope (Konan Medical, Inc) modified by removal of the chin rest to allow use on horizontal patients. The study included 2 parts with 2 different cohorts. The first part, assessing intersession and intrasession variability, included acquiring 4 images (images 1A, 1B, 2, and 3) in the lateral decubitus position. Images 1A and 1B were taken in the same session and images 2 and 3 were taken after repositioning the patient’s head, simulating 2 different sessions. The second part served to compare SM images of the same eye taken while awake in the upright position (fixating eye) and then in the lateral decubitus position under GA (nonfixating eye). Intraclass correlation and Bland-Altman analysis with 95% limits of agreement were used to assess agreement between sessions. The study was approved by the Research Ethics Board of The Hospital for Sick Children, Toronto, Ontario, Canada. All patients’ guardians provided written informed consent.

Results

Fifteen eyes of 15 patients and 16 eyes of 16 patients were recruited for the first and second parts of the study, respectively. The mean (SD) age was 5.7 (4.5) years (range, 1-14 years) for part 1 and 9.1 (3.4) years (range, 4.3-18 years) for part 2. Part 1 included 8 boys and 7 girls; part 2 included 12 boys and 4 girls. No difference in mean endothelial cell density (ECD) between the different sessions was identified (Table). Mean percentage ECD differences were small and ranged from 2.6% (95% CI, 1.6%-3.8%) to 4.4% (95% CI, 3.0%-5.7%). Comparison of the technique using the nonfixating eye while the patient was under anesthesia vs the gold-standard acquisition technique using the same eye while fixating showed a mean (SD) ECD difference of 98.8 (66.5) cells/mm2 (95% CI, 65.3-132.2 cells/mm2). Bland-Altman plots demonstrating the relationship between the differences in measurement and the mean measurement value of the 2 techniques with 95% limits of agreement are shown in the Figure.

Discussion

Investigation of the corneal endothelium in children has been hampered by an inability to image this layer reliably. Because the endothelium is known to be affected by both cataract and glaucoma surgery, the ability to assess ECD in children is of great clinical relevance. Speedwell et al4 described the use of a contact specular microscope in infants younger than 12 months for acquiring endothelial images in the lateral decubitus position. The equipment they used is no longer available and the technique was never validated against fixating eye measurements. To our knowledge, no further in vivo studies have been published on the infant endothelium.

In a study by Benetz et al5 for the Cornea Donor Study Group, the interobserver variance standard was set at a level below 5% for excellent-quality images. Our mean percentages of intersession and intrasession variability and our mean percentage of variability between the fixating and nonfixating imaging techniques were 4.4% or less. In addition, our intraclass correlation values reflected excellent agreement for all comparisons. Our calculated 95% limits of agreement for the different comparisons are lower than reported in the literature.6 This study demonstrates that SM images of high quality obtained in children during GA are interchangeable with those taken while children are awake. This will allow prospective study of the endothelium in children over time and in response to disease and surgery.

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Article Information

Corresponding Author: Uri Elbaz, MD, Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, University of Toronto, 555 University Ave, Toronto, ON M5G 1X8, Canada (urielbaz@gmail.com).

Published Online: October 8, 2015. doi:10.1001/jamaophthalmol.2015.3695.

Author Contributions: Drs Elbaz and Ali had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Elbaz, Mireskandari, Ali.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Elbaz, Mireskandari.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Elbaz.

Obtained funding: Mireskandari, Ali.

Administrative, technical, or material support: Ali.

Study supervision: Mireskandari, Ali.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Ali reported receiving a grant from Physicians’ Services Incorporated Foundation outside this work. No other disclosures were reported.

Funding/Support: This work was supported in part by Brandan’s Eye Research Foundation.

Role of the Funder/Sponsor: Brandan’s Eye Research Foundation had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

References
1.
Sherrard  ES, Novakovic  P, Speedwell  L.  Age-related changes of the corneal endothelium and stroma as seen in vivo by specular microscopy. Eye (Lond). 1987;1(pt 2):197-203.PubMedArticle
2.
Bahn  CF, Glassman  RM, MacCallum  DK,  et al.  Postnatal development of corneal endothelium. Invest Ophthalmol Vis Sci. 1986;27(1):44-51.PubMed
3.
Kaufman  HE, Capella  JA, Robbins  JE.  The human corneal endothelium. Am J Ophthalmol. 1966;61(5, pt 1):835-841.PubMedArticle
4.
Speedwell  L, Novakovic  P, Sherrard  ES, Taylor  DS.  The infant corneal endothelium. Arch Ophthalmol. 1988;106(6):771-775.PubMedArticle
5.
Benetz  BA, Gal  RL, Ruedy  KJ,  et al; Cornea Donor Study Group.  Specular microscopy ancillary study methods for donor endothelial cell density determination of Cornea Donor Study images. Curr Eye Res. 2006;31(4):319-327.PubMedArticle
6.
de Sanctis  U, Machetta  F, Razzano  L, Dalmasso  P, Grignolo  FM.  Corneal endothelium evaluation with 2 noncontact specular microscopes and their semiautomated methods of analysis. Cornea. 2006;25(5):501-506.PubMedArticle
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