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 Table of Contents  
Year : 2019  |  Volume : 112  |  Issue : 2  |  Page : 61-66

Evaluation of type 2 diabetes mellitus effect on human cornea using specular microscopy and Pentacam corneal tomography

1 Resident of Ophthalmology at Ophthalmology Hospital in Sohag, Faculty of Medicine, Ain Shams University
2 Professor of Ophthalmology, Opthalmology Department, Faculty of Medicine, Ain Shams University
3 Assistant professor of ophthalmology, Opthalmology department, Faculty of medicine, Ain Shams University

Date of Submission11-Mar-2019
Date of Acceptance13-Mar-2019
Date of Web Publication19-Jul-2019

Correspondence Address:
Amal Atef Salah Taha
Resident of Ophthalmology at Ophthalmology Hospital in Sohag

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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ejos.ejos_15_19

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Purpose evaluating effect of type 2 DM using pentacam and specular microscopy, and correlate changes to DM and its control.
Methods A randomized cross sectional study . Ninty eyes of 45 patients were examined by pentacam HR; where elevation based "anterior corneal elevation (ACE)" and "PCE" and thickness based "TCT" and "ARTmax" indices were recorded and Specular Microscopy were "ECD" and "CV" indices were evaluated . Corneas were categorized into 3 groups according to HBA1C level; group 1 (30eyes) with uncontrolled DM,group 2 (30eyes) with controlled DM,while group 3 (30 eyes) with healthy controls. Possible effect of DM on the forementioned indices was evaluated and a correlation between HBA1C and these indices was investigated.
Results regarding Pentacam elevation indices (ACE, PCE), PCE showed a significant increase in group 1 compared to group 3 (p-value=0.005), while ACE showed a significant increase between group 2 and each of group 1 (p-value =0.031) and group 3 (p-value=0.025). AS regard to pachymetric indices, TCT and ART max showed a significant difference between group 1 and group 3 (p=0.001 and 0.048). Specular Microscopy indices; ECD showed a significant difference between each of (group 1, group 2) diabetics and group 3 (p=0.001), while CV showed a significant increase in group 1 compared to group 3 (p=0.005). Regression analyses showed positive correlations between HBA1C and each of PCE, TCT, ART max, ECD, CV.
Conclusion Some pentacam indices showed significant changes with variations in HBA1C level ,which are sensitive indices in ectasia detection. Regular follow up of type 2 diabetics by performing pentacam is recommended, especially for uncontrolled DM.

Keywords: ACE, CV, DM, ECD, PCE, pentacam

How to cite this article:
Taha AS, Salman AG, Mohammed TH, Elkitkat RS. Evaluation of type 2 diabetes mellitus effect on human cornea using specular microscopy and Pentacam corneal tomography. J Egypt Ophthalmol Soc 2019;112:61-6

How to cite this URL:
Taha AS, Salman AG, Mohammed TH, Elkitkat RS. Evaluation of type 2 diabetes mellitus effect on human cornea using specular microscopy and Pentacam corneal tomography. J Egypt Ophthalmol Soc [serial online] 2019 [cited 2020 Aug 15];112:61-6. Available from: http://www.jeos.eg.net/text.asp?2019/112/2/61/263006

  Introduction Top

Corneal evaluation is an important tool in ophthalmologists’ daily practice. In fact, physicians rely on corneal parameters, including corneal thickness, anterior and posterior curvatures, anterior chamber depth or endothelial cell count for proper diagnosis, follow-up or plotting treatments, either for refractive errors or many ocular diseases, such as glaucoma, corneal ectasia, or cataract [1].

Hyperglycemia is a metabolic condition that can have damaging effects on almost all body tissues. Ophthalmic complications of hyperglycemia are most notable in the cornea and the retina. Retinal impairment is responsible for the majority of visual impairments in diabetics; however, corneal impairment remains a major vision-hindering pathology [2].

Diabetes mellitus (DM) has a significant effect on the morphology, physiological aspects, and clinical corneal condition. The diabetic tear film is composed of a four-fold higher glucose content than that of normal tear film. Changes can also be detected at the corneal epithelium, basement membrane complexes, stroma, and the endothelium [3].

Literature showed that eyes of diabetics usually develop a higher central corneal thickness (CCT), and that correlations exist between CCT and the degree of diabetic retinopathy [4]. Corneal hydration control has also been shown to be affected in diabetic corneas [5].

The Pentacam corneal tomography is a noncontact modality that uses a rotating Scheimpflug camera to capture scans of the anterior segment. It allows measurement of corneal thickness from limbus to limbus, besides the assessment of anterior and posterior corneal elevations. New indices are being introduced in corneal evaluation, with the literature discussing the accuracy of various indices for ectasia detection [6].

Specular microscopy is a noncontact instrument that can evaluate both corneal pachymetry and specular microscopy simultaneously, visualizing endothelial morphology and cell density [7].

Global evaluation of diabetic corneas, using both specular microscopy and Pentacam Scheimpflug camera, can give us meticulous and integrative data regarding the impact of DM on human corneas.

  Patients and methods Top

This is a randomized, cross-sectional study that included 90 eyes of 45 participants, with 60 eyes of 30 patients having DM type 2 and following up at the Internal Medicine Clinic of Sohag University, and 30 eyes of 15 participants as age-matched and sex-matched healthy participants. The study was performed in the time interval between December 2017 and December 2018. The study was conducted as per the ethical standards of the Ethics Committee of Ain Shams University Hospitals, with informed consents explained and signed by all participants. We excluded candidates with any detected corneal pathology, contact lens wear within 2 weeks interval, narrow palpebral fissure hindering proper scanning, previous ocular surgeries, and any associated systemic disease.

Candidates were categorized into three groups according to glycosylated Hb (HbA1c) level; group 1 (30 eyes) included patients with uncontrolled type 2 DM (HbA1c>7.5%), group 2 (30 eyes) enrolled patients with controlled type 2 DM (HbA1c between 6 and 7.5%), while group 3 was for age-matched and sex-matched healthy participants (HbA1c<6%).

History taking from the participants was followed by ophthalmic examination, including uncorrected visual acuity and best corrected visual acuity, slit-lamp examination, slit-lamp biomicroscopy, and Goldmann’s applanation tonometry.

All enrolled eyes were scanned by Pentacam HR branded as Allegro oculyzer II (WaveLight GmbH, Erlangen, Germany). Each eye was scanned as per the instructions of the device manual, and the most reliable scan was chosen according to the largest analyzed area, valid data percentage, and proper alignment. Analysis was performed using device software version 20.0. The investigated indices included:
  1. Elevation-based indices (obtained from Belin Ambrosio Enhanced Ectasia display/Difference maps): (a) anterior elevations from best fit sphere (BFS) and (b) posterior elevations from BFS.
  2. Pachymetry-based indices (obtained from Belin Ambrosio Enhanced Ectasia display/Difference maps): (a) thinnest corneal thickness (TCT) and (b) Ambrosio relational thickness index (ARTmax).

Afterwards, all the recruited participants were examined by specular microscopy (SP-3000 P; Topcon, Tokyo, Japan). The patient’s head was properly positioned, and the patient was instructed to look into the fixation target. Automatic focusing was used to capture an accurate scan. Automated cell analysis was used to evaluate all the parameters.

Parameters of the endothelium were assessed including: endothelial cell density (ECD) and coefficient of variation (CV).

Statistical analysis

The recorded data were analyzed using the statistical package for the social sciences, version 20.0 (SPSS Inc., Chicago, Illinois, USA). Quantitative data were expressed as mean±SD. Qualitative data were expressed as frequency and percentage. A one-way analysis of variance (ANOVA) when comparing between more than two means and post-hoc test were used for multiple comparisons between different variables
  1. The P value was considered significant as the following:
  2. P value:
    1. P value up to 0.05 was considered significant.
    2. P value up to 0.001 was considered as highly significant.
    3. P value more than 0.05 was considered insignificant.

  Results Top

Regarding the participants’ demographic data, including age, sex and laterality, there were no detected differences among groups ([Table 1]).
Table 1 Comparison between groups regarding demographic data

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On evaluating HbA1c level, one-way ANOVA test resulted in highly significant differences (P<0.001). Post-hoc test showed a difference between each of group 1 and group 2 (P<0.001), group 1 and group 3 (P<0.001), and group 2 and group 3 (P=0.044).

Regarding best corrected visual acuity and uncorrected visual acuity, no detected differences were shown among the studied groups.

As regards intaocular pressure (IOP) and slit-lamp examination, they were normal with unremarkable results.

Pentacam indices evaluation

Elevation-based indices

Regarding anterior corneal elevation (ACE); one-way ANOVA test showed a significant difference among groups (P=0.040); post-hoc test resulted in a difference between each of group 1 and group 2 (P=0.031) and group 2 and group 3 (P=0.025; [Table 2]).
Table 2 Comparison between groups according to ACE

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PCE, one-way ANOVA test showed significant difference among groups (P=0.019), while post-hoc test showed a difference between uncontrolled diabetics and normal participants (P=0.005; [Table 3]).
Table 3 Comparison between groups regarding PCE

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Pachymetry-based indices

About TCT, there was a significant difference among groups by ANOVA test (P=0.001), while post-hoc test resulted in a difference between each of group 1, group 3 and group 2, group 3 (P<0.001; [Table 4]).
Table 4 Comparison between groups regarding thinnest corneal thickness

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ARTmax; ANOVA showed a significant difference among groups (P=0.049), while post-hoc test showed a difference between uncontrolled diabetics and normal participants (P=0.048; [Table 5]).
Table 5 Comparison between groups according to Ambrosio relational thickness maximum

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Regarding specular microscopy indices

On evaluating ECD, ANOVA test showed a difference among groups (0.001); post-hoc test showed a significant difference between each of group 1 and group 3 and group 2 and group 3 (P<0.001; [Table 6])
Table 6 Comparison between groups according to endothelial cell density

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CV, one-way test showed a significant difference among groups (P=0.042); while post-hoc test resulted in a significant difference between group 1 and group 2 (P=0.047), group 1 and group 3 (P=0.037), and group 2 and group 3 (P=0.005; [Table 7]).
Table 7 Comparison between groups according to coefficient of variation%

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We have performed regression analyses between HbA1c and each of the examined parameters of Pentacam and specular microscopy, which showed significant correlations between HbA1c% and each of TCT, PCE, ARTmax, CV%, and ECD with a P value of 0.009, 0.012, 0.008, 0.011, and 0.002, respectively.

  Discussion Top

Corneal changes are present in about 70% of patients with diabetes, as the diabetic cornea has cellular dysfunction which include recurrent erosions, delayed wound healing, ulcers, and edema. In addition, changes in epithelial basement membrane occur. Also, neuropathy occurs in diabetic cornea, leading to loss of corneal sensation and innervation [8].

In the body, the reaction (Maillard reaction) between reducing sugars and/or carbonyls with free amino groups shares in the formation of advanced glycation end products (AGEs), and these substances may then accumulate intracellularly and extracellularly on proteins, lipids, and nucleic acids [9].

In this study, we investigated the possible effects of DM type 2, either controlled or uncontrolled (as denoted by HbA1c level) on the recruited corneas. Pentacam and specular microscopy were chosen for the evaluation of various selected corneal parameters. To enforce our results, we plotted regression analyses to assess the possible correlation between HbA1c and all evaluated parameters. Pentacam evaluated indices included elevation-based indices (ACE, PCE) and pachymetry-based indices (TCT, ARTmax). To our knowledge, this is the first study to evaluate the effect of DM on those parameters. As regards specular Microscopy parameters, we evaluated CV and ECD.

In this study, a highly significant increase in TCT was found in controlled and uncontrolled diabetics compared with healthy participants (P<0.001). The regression analyses showed a positive correlation between HbA1c and TCT (P=0.009). Most of the studies about corneal parameters in DM evaluated CCT, some suggested that CCT could be the earliest change in diabetic eyes [10]. Roszkowaska et al. [11] stated in their study that there is a remarkable increase in CCT. Another study by Modis et al. [12] showed that diabetic corneas are thicker than normal participants. We can correlate these changes to corneal edema occurs in as DM which reduces the activity of Na-K-ATPase of the ionic pump of corneal endothelium and this causes the structural and permeability changes of the cornea as detected by Saini et al. [13]. Another possible mechanism of corneal edema is accumulation of glycosylated material on corneal stroma [14].

In this study, we found a significant increase in ACE in controlled diabetic patients compared with healthy participants and uncontrolled DM (P=0.025 and 0.031, respectively), while no significant increase was detected between uncontrolled diabetic patients and normal participants (P=0.9). Since the change in ACE was significant between healthy participants and controlled diabetics rather than uncontrolled diabetics, the change could be attributed to causes other than DM. Furthermore, these significant differences were weakened by the negative correlation between HbA1c and ACE.

We may also attribute the increase in ACE in controlled rather than uncontrolled diabetic patients to the accumulation of AGEs in uncontrolled diabetic patients which has been suggested to form AGE-mediated cross‐linking that decreases elevation indices.

Cross-linking in keratoconus decreases elevation indices as a study by Grewal et al. [15] on patients who underwent CXL to treat keratoconus showed a decrease in anterior and posterior elevations after the end of the 12-month follow-up.

As regards PCE, there was a significant difference between uncontrolled DM and healthy participants (P>0.005). Furthermore, regression analyses showed a positive correlation between HbA1c and PCE (P=0.012). This denotes a possible established effect of elevated blood sugar levels in uncontrolled DM type 2 on PCE.

Moreover, on evaluating ARTmax, there was a significant difference between uncontrolled DM and healthy participants (P=0.048), with decreased values in diabetic patients. Assessment of regression analyses showed a positive correlation between HbA1c and ARTmax (P=0.008).

PCE and ARTmax are the most sensitive indices for early ectasia development [16]. Furthermore, TCT increases in diabetics compared with controls augments the increased risk of ectasia, being also one of the sensitive indices in ectasia [17].

We evaluated ACE and PCE from the difference map of the Belin Ambrosio display, but most studies evaluate these indices from best fit sphere or best fit toric ellipsoide [16]; however, we evaluated indices from difference maps as they are supposed to be sensitive indices in ectasia evaluation as they negate the possible effect of the highest values from the corneal surface.

It has been proposed that AGE-mediated cross‐linking could have benefits for stiffening the weakened cornea of diabetic patients with keratoconus [14]. However, this study showed affection of PCE and ARTmax indices, which increases the risk of ectasia in diabetic patients [20].

As regards specular microscopy indices, this study confirms the previous studies ̓ results. On evaluation of ECD, there is a highly significant difference between uncontrolled DM and healthy participants (P<0.001) with decreased values in diabetic patients. Furthermore, regression analyses showed a positive correlation between HbA1c and ECD (P=0.002). Studies performed by Inoue and coworkers [18] resulted in reduced ECD. Roszkowaska et al. [11] showed that the endothelium of the cornea is the tissue under metabolic stress in diabetics. Another study by Lee [19] resulted in the same changes about ECD. SU [4] showed the same results about ECD. All these studies are in accordance with our results regarding ECD. Shenoy et al. concluded that examination of ECD should be routine in diabetic patients.

On evaluating CV in this study, there was a significant increase in diabetic patients compared with normal participants (P=0.005); moreover, regression analyses showed a positive correlation between HbA1c and CV (P=0.01). This is in accordance with a study by Lee and Welson [19]. No studies showed a decrease in CV in diabetic patients.

Further studies with a higher sample size and with evaluation of other sensitive indices for ectasia detection are required.

  Conclusion Top

Type 2 DM has its tomographic and morphologic impact on the human cornea. Changes in CV and ECD were detected. Pentacam tomographic indices showed significant changes with variations in HbA1c level, mainly in PCE, ARTmax, and TCT, which are sensitive indices in ectasia detection. Hence, although self-cross-linking has been proposed in diabetic corneas, to our knowledge, ours is the first study to detect possible early ectatic changes. Regular follow-up of type 2 diabetic patients by performing Pentacam corneal tomography is recommended, especially for uncontrolled type 2 DM.

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Conflicts of interest

There are no conflicts of interest.

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  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]


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