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Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."
Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011
Dr. Shankar P.R.
"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."
Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011 Anuradha
Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.
Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020
Original article / research
Full Version
Corneal Endothelial Morphology and Central Corneal Thickness Changes in Type 2 Diabetes Mellitus using Specular Microscopy and Ultrasonic Pachymetry: A Cross-sectional Comparative Study
Correspondence Address :
Dr. Prakriti Chourasia,
E-58, 1st Floor, C/O Kapoors, Bali Nagar, Delhi, India.
E-mail: pcdelhi@yahoo.com
Introduction: Diabetes Mellitus (DM) is a metabolic condition characterised by chronic hyperglycaemia, causing raised blood glucose levels which result in microvascular and macrovascular disorders and may introduce ocular manifestations including changes in corneal Endothelial Cell Density (ECD), corneal thickness, and intraocular pressure. It is clinically important to analyse the corneal endothelial status in patients with type II DM as preoperative corneal endothelial cell dysfunction may cause more corneal endothelial cell damage postoperatively leading to corneal decompensation. With the advent of precise and better measurement tool Central Corneal Thickness (CCT) and corneal endothelial morphology measurement has become more accurate.
Aim: To compare corneal endothelium cell density, polymorphism, polymegathism and CCT in type 2 DM with age-matched, non diabetic control subjects using CEM-530 Specular microscope and ultrasonic pachymeter Tomey SP-100.
Materials and Methods: This cross-sectional, comparative study was conducted at Eye Department at ESI Post Graduate Institute of Medical Sciences and Research, Basaidarapur, Delhi, India, from October 2018 to November 2019 on a total of 150 patients. Seventy five known type 2 DM patients were enrolled in diabetic group (case group) and 75 non diabetic, age-matched subjects were enrolled as control group. Cases were classified under three major groups, namely on the basis of duration of DM and severity of Diabetic Retinopathy (DR) and glycaemic control {glycosylated haemoglobin (HbA1c) level}. All the findings were endorsed on a predesigned performa. Statistical Package for Social Sciences (SPSS) version 17.0 was used for analysis of data.
Results: Among the 150 patients evaluated, type 2 DM patient’s corneas (540.51±32.578 μ) were thicker as compared to control group 517.51±22.155 μ(p-value <0.001). The mean ECD of control and diabetic group patients was 2723.75±287.253 cells/mm2 and 2716.11±296.081 cells/mm2, respectively, found insignificant (p-value=0.821). The mean Coefficient of Variation (CV) of cell area of control and diabetic patients was 28.87±3.950 and 29.85±4.027, respectively, and was significant (p-value=0.034). The mean percentage of endothelial Hexagonal cells (HEX%) of control and diabetic patients were 67.39±6.419 and 67.41±5.493, respectively and was non significant (p-value=0.985). Thus, statistically significant difference was found with CCT (p-value <0.001) and CV (p-value=0.034) but not with ECD and hexagonality, between control and diabetic eyes. There was a correlation between CCT, CV, HEX% and ECD with duration of DM2 but it was statistically insignificant. There were higher CCT, CV and HEX% and lower ECD in >10 years of duration of diabetes mellitus than in patients with duration of diabetes mellitus ≤10 years. There was a correlation of CCT, CV, ECD and HEX with HbA1c level. There were significant higher CCT and CV values in >7% HbA1c level group than in group with ≤7% HbA1c level. There was also increased ECD in >7% group, but it was found to be insignificant. Percentage of hexagonality in >7% HbA1c level group was lower than in group with ≤7% HbA1c level, but found insignificant. There were higher values of CCT and CV in Non Proliferative Diabetic Retinopathy (NPDR) subgroup compared to Proliferative Diabetic Retinopathy (PDR) and no Diabetic Retinopathy group.
Conclusion: The present study documented that DM has considerable effects on all the layers of the cornea especially endothelial layer, causes reduction of ECD and increased CV. Diabetic cornea has increased CCT and lower percentage of hexagonal cells than normal subjects. In addition, there is a correlation between the changes in corneal parameters like ECD, CV, HEX%, CCT with the duration of DM and severity of DR and glycaemic control {glycosylated haemoglobin (HbA1c) level}.
Coefficient of variation, Diabetic retinopathy, Endothelial cell density, Glycosylated haemoglobin, Hexagonality
The Diabetes Mellitus (DM) is a metabolic condition characterised by chronic hyperglycaemia subsequently causing raised blood glucose levels which results in microvascular and macrovascular disorders and may introduce ocular manifestations including changes in corneal Endothelial Cell Density (ECD), corneal thickness, and intraocular pressure (1). The prevalence of diabetes is estimated to be about 6.4% worldwide, and in the past two decades alone there has been a dramatic increase in the diagnosis of type II DM (2).
The DM is one of the chief causes of blindness globally and can affect eye leading to ocular problems including Diabetic Retinopathy (DR), cataracts, keratopathy, glaucoma (3). Clinical evidence shows that patients with type II diabetes present alterations, such as increased epithelial fragility and recurrent erosions, reduced sensitivity, impaired wound healing, altered epithelial barrier function, and persistent stromal oedema after intraocular surgical procedures (4),(5).
Corneal endothelial cells are organised in a monolayer. At birth, Corneal Endothelial Cell Density (CED) ranges from 4000-5000 (cells/mm2). With age, it regresses at a rate of 0.3-0.6% per year and reaches approximate range of 2000-3000 cells/mm2 in a normal adult eye (6),(7). CED decreases with age, trauma, refractive surgery, intraocular surgery, glaucoma, corneal dystrophies and DM (7). Central Corneal Thickness (CCT) is another important parameter for corneal health as the Intraocular Pressure (IOP) depends on corneal thickness and CCT must be taken into consideration in evaluating glaucoma patients or suspects (8). Human corneal endothelial cells do not regenerate after injury but heal through their hyperplasia and mobilisation (9).
Various studies suggest that, in diabetes cornea, there is decrease in ECD and polymorphism (cell shape variation) means decrease in the percentage variation) which means increased Coefficient of Variation (CV) of cell area (CV values measured between 0.22 and 0.31 are considered normal and above 0.4 are abnormal) along with increased CCT (1),(10),(11),(12). Few studies suggest clinical importance of CCT assessment for diagnosing intraocular pressure pathologies and ECD evaluation to determine the compromise of the endothelial barrier function (13),(14).
The hypothesis of the study was that type 2 DM causes decrease reduction of ECD, along with lower percentage of hexagonality (polymorphism), increased CV (polymegathism) and increased CCT as compared to age matched non diabetic subjects. There is paucity of Indian studies carried out in relation with this topic, so this study is an attempt to fill the gap. The primary objective of this study was to compare corneal ECD, CV, percentage of endothelial hexagonal cells (HEX%) and CCT in type 2 DM with age-matched, non diabetic control subjects using CEM-530 Specular Microscope and ultrasonic pachymetry Tomey SP-100.
The secondary objective of the study was to assess correlation between the changes in above mentioned corneal parameters and the duration of DM, severity of DR and glycaemic control {glycosylated haemoglobin (HbA1c) level}.
This cross-sectional, comparative study was conducted at Eye Department at ESI Post Graduate Institute of Medical Sciences and Research, Basaidarapur, Delhi, India, from October 2018 to November 2019. Patients with ages between 40-70 years of either gender who were diagnosed to have DM were recruited in the study, after approval by Ethical Review Committee of Hospital (DM/A91-9/14/17/IEC/2012-PGIMSR) (PART-II). Informed and written consent was obtained from each subject before enrollment.
Sample size calculation: To calculate the number of participants needed for this study, the significance level was set at 95% (α=0.05), and the power of the test was set at 80% with a type II error (β) of 0.20. A previous study by El-Agamy A and Alsubaie S, found that mean ECD in the control group was 2660.1±515.5 (15). Assuming that ECD width decreases in type II diabetic patients, sample size of 35 eyes per group was calculated:
n=(σ12+σ22). (Z 1-α/2+Z 1-β)2/(M1-M2)2
=(515.52+515.52). (1.96+1.282)2/(399.02*399.02)
=(265740.3+265740.3)*10.51/159213=65.08
Where,
Zα/2 is the critical value of the Normal distribution at α/2 (e.g., for a confidence level of 95%,
α is 0.05 and the critical value is 1.96),
Zβ is the critical value of the normal distribution at β (e.g., for a power of 90%, β is 0.1 and its critical value is 1.282)
σ 1 and σ 2 are the standard deviations of the two groups and M1 and M2 are the means of two groups.
After calculating minimum sample size for present study to get the statistically significant results, minimum participants required for this study were 65 and hence:
Diabetic group (n=75 cases, 150 eyes): Cases were classified under three major groups, namely on the basis of duration of DM, severity of DR and glycaemic control (glycosylated haemoglobin level):
• Duration of DM with ≤10 years of the disease or >10 years of the disease.
• Presence or absence of Diabetic Retinopathy (DR) and patients having DR were further classified into three subgroups:
Patients having no DR
Patients with Non Proliferative Diabetic Retinopathy (NPDR)
Patients with Proliferative Diabetic Retinopathy (PDR)
• Glycosylated Haemoglobin (HbA1c) levels of the patients ≤7.0% or >7.0% at the time of presentation (American Diabetes Association) (16).
Control group (n=75 subjects, 150 eyes): Age-matched non diabetic subjects formed the group.
All patients were recruited by non randomised convenience sampling method.
Inclusion criteria: Cases were patients aged between 40-70 years of either gender, and diagnosed case of type 2 DM. Diagnosis of DM was based on criteria of the American Diabetes Association (16). Controls were age-matched non diabetic subjects.
Exclusion criteria: Patients with presence of history of past ocular or intraocular surgery, corneal disease (dystrophies) or any signs of previous corneal disease (corneal opacity), ocular inflammation or trauma, previous retinal photocoagulation laser and anti-vascular endothelial growth factor therapy injection, contact lens wearer, glaucoma, pterygium, entropion or trichiasis, rheumatoid arthritis and systemic lupus erythematous that are known to impair tear function were excluded from the study.
Age, gender, duration of diabetes, level of HbA1c, severity of DR, current medical treatment, other systemic co-morbidities such as rheumatoid arthritis, systemic lupus erythematous that are known to impair corneal morphology along with impaired tear function.
Study Procedure
All subjects underwent following complete ophthalmic examination which included, visual acuity assessment using Snellen chart following refractive acceptance. Intraocular pressure (mmHg) measurement using Goldmann applanation tonometer, slit-lamp biomicroscopy and Fundus examination by 90D biomicroscopy and indirect ophthalmoscope.
• The corneal endothelial parameters: ECD (cell/mm2), hexagonality (HEX%), CV measured using specular microscope (CEM-530; NIDEK) by a single examiner.
• Central Corneal Thickness (CCT) (μm) was measured by ultrasonic pachymetry (Tomey SP-100). Measurements were taken three times in the centre of cornea. An average of three readings was used for final analysis.
Statistical Analysis
Statistical Package for Social Sciences (SPSS) version 17.0 was used for analysis of data. Continuous variables, presented as mean±SD, and categorical variables, presented as absolute numbers and percentage. Age and corneal parameters (ECD, CCT, CV and HEX%) compared using unpaired t-test in diabetic and control group. Also, for comparison in between subgroup of diabetic patients on HbA1c level done by using Analysis of Variance (ANOVA) test. Comparison among gender (male and female) done by using Chi-square test. Corneal parameters (ECD, CCT, CV and HEX%) was correlated using Pearsons correlation test. Independent t-test is used to compare the variables between the duration of diabetes disease <10 years and >10 years. Right and left eye parameters were compared using paired t-test in diabetic group and control group separately. The level of significance was set at p-value ≤0.05.
A total of 150 subjects that met the inclusion criteria and exclusion criteria were included in the study. As shown in (Table/Fig 1), mean age was 52.8±8.77 years in control group and 53.25±8.36 years in diabetic group (p-values=0.746; unpaired t-test).
In the present study population, there were 40 (53.3%) male with mean age of 53.4±8.65 years and 35 (46.7%) female with mean age of 53.09±8 years in diabetic group. A 42 (56.0%) male with mean age of 51.31±7.38 years and 33 (44.0%) female with mean age of 54.7±9.94 years in control group, statistically non significant (p-value=0.743) (Table/Fig 2).
As shown in (Table/Fig 3), 102 eyes found to have no diabetic changes in retina, 40 eyes had NPDR while eight eyes had PDR. An analysing duration of DM2, 55 patients (110 eyes) had history of <10 years and 20 patients (40 eyes) had history of >10 years. Among the 75 diabetic patients, 37 patients (74 eyes) found to have HbA1c levels less than 7% and 38 patients (76 eyes) had HbA1c levels more than 7%.
Spectrometry and Pachymetry Data Evaluation
The mean CCT of control and diabetes group patients was 517.51±22.155 microns and 540.51±32.578 microns, respectively and was significant (p-value <0.001). The mean ECD of control and diabetes group patients was 2723.75±287.253 cells/mm2 and 2716.11±296.081 cells/mm2, respectively and difference was not significant (p-value=0.821). The mean CV of control and diabetes group patients was 28.87±3.950 and 29.85±4.027, respectively and difference was found significant (p-value=0.034). The mean HEX% of control and diabetes group patients was 67.39±6.419 and 67.41±5.493, respectively and difference was not significant (p-value=0.985) (Table/Fig 4). The ECD values were found to be on higher side in control eyes than diabetic eyes but this difference was statistically insignificant. Likewise, statistically insignificant difference was noted with HEX% but with slightly increased value in diabetic patients.
Duration of DM and corneal parameters: Eyes with DM duration of ≥10 years showed higher CCT (543.70±25 μm), patients with DM ≤10 years (539.35±34 μm), statistically non significant (p-value=0.471). ECD was higher in patients with DM ≤10 years (2722.48±28 cells/mm2) (p-value=0.663). The CV was higher in patients with DM ≥10 years group (29.90±4.2) as compared to patient with DM ≤10 years group (29.84±3.9) (p-value=0.932). No statistical significance in HEX% between the two groups (p-value=0.161) (Table/Fig 5).
HbA1c and and corneal parameters: The CCT was higher and significant among patients with HbA1c >7% (546.58±30.10 μm) as compared to patients with HbA1c ≤7% group (534.27±34.02 μm) (p-value=0.020). The HEX% (p-value=0.681) and ECD (p-value=0.703) between the two groups was statistically insignificant but CV between the two groups was statistically significant (p-value=0.006) (Table/Fig 6). There was higher values of ECD in eyes with HbA1c >7% than HbA1c <7% eyes, but this result was statistically insignificant.
Diabetic retinopathy and corneal parameters: Comparison of CCT among diabetic patients using One-way ANOVA test showed that the mean value CCT in eyes with NPDR (554.20±26.912 μ) was highest followed by eyes not having any DR (535.60±34.001 μ) and least in PDR eyes (534.63±20.340 μ), difference was found to be statistically significant (p-value=0.007). The mean value of ECD in eyes with NPDR (2637.05±301.580 cells/mm2) was lowest followed by PDR eyes (2744.38±299.488 cells/mm2) and highest in eyes not having any DR (2744.89±290.886 cells/mm2), found to be statistically insignificant (p-value=0.143). The mean value of CV in eyes with NPDR (31.65±4.560) was highest followed by eyes not having any DR (29.37±3.609) and least in PDR eyes (27.00±3.207), found to be statistically significant (p-value=0.001). The mean value of hexagonality in eyes with PDR (72.00±4.472%) was highest followed by NPDR eyes (67.28±5.325%) and lowest in eyes not having any DR (67.10±5.514%), found to be statistically significant (p-value=0.050) (Table/Fig 7).
The Pearson correlation coefficient analysis showed that DM duration had no significant correlation with CCT, CV, HEX% and ECD.
Correlation: The Pearson’s correlation coefficient analysis showed that DM duration had no significant correlation with CCT, CV, HEX% and ECD. The Pearson’s correlation coefficient between HbA1c value and CCT was significant (p-value <0.001). Similarly, Pearson’s correlation coefficient between HbA1c value and CV was significant (p-value=0.003). The Pearson correlation coefficient between HbA1c value and ECD (p-value=0.505) was insignificant. The corneal hexagonality had negative Pearson correlation coefficient with HbA1c for both eyes and this was statistically non significant. In case of diabetic patients there was a weak correlation between CCT and CV; and CV and ECD. HEX% was significant (p-value=0.012) with respect to CCT in diabetic patients. In control group, there was a negative correlation between CV and HEX% and there was a positive correlation ECD and HEX% (Table/Fig 8),(Table/Fig 9),(Table/Fig 10),(Table/Fig 11).
The DM is a chronic metabolic disorder. Corneal endothelium of diabetic cornea may suffer from many morphological changes. It is clinically important to analyse the corneal endothelial cell morphology in patients with type 2 diabetes, undergoing any intraocular surgical procedure like cataract or glaucoma surgeries. Postoperative corneal endothelial cell loss leads to corneal decompensation. This further leads to corneal endothelial cell transplantation. Thus, highlighting the importance of preoperative measurements of CCT, CV, ECD and HEX%.
In the present study, statistically significant difference was found with CCT (p-value <0.001) and CV (p-value=0.034) but not with ECD and hexagonality, between control and diabetic eyes. Higher values of CCT and CV in diabetic eyes were witnessed in this study. ECD values (p-value=0.821) were found to be on lower side in diabetic eyes than control and differences were statistically insignificant. Likewise, statistically insignificant differences were noted with HEX% (p-value=0.985) but with slightly increased value in diabetic patients.
In a similar study done by Schultz RO et al., 46 corneas of 25 type 2 DM patients with duration of >10 years were examined by specular microscopy (17). There was no difference in ECD and CCT but revealed a considerably higher CV and reduction in the percentage of hexagonal cells, in comparison non diabetic population (n=21). Similarly in the present study, it was found that there was no significant difference in the ECD (p-value=0.821) and significant difference in the CV (p-value=0.034) in type 2 DM patients in comparison to control subjects. But to the contrary, difference in the HEX% (p-value=0.985) was found insignificant. Schultz RO et al., also showed that the coefficient of variation has a significant inverse relationship with the frequency of hexagonal cells and the figure coefficient (17). Present study also found same correlation between CV and HEX% (Pearson’s Correlation=-0.392, p-value <0.0001).
The underlying reason of this difference in results in the percentage of hexagonal cells could be dissimilarity in the duration of diabetes in case arm. In present study both >10 years and <10 years of duration of disease patients were taken while in Schultz RO et al., study only >10 years of duration of disease patients were included (17).
Larsson L et al., studied 60 known patients of type 2 DM and they found no difference in cell density among type 2 DM patients and control groups (18). Type 2 DM patients had decreased HEX%, increased CV and increased CCT but they did not differ significantly from controls. The type II diabetics were older than the type I diabetics, and the older control group showed changes similar to those seen in the diabetics; these changes were presumably associated with aging. In contrast to this study, findings were significantly different in CCT and CV among type 2 DM patients and control groups, in present study. But HEX% was found lower in type 2 DM patients as in Larsson L et al., study (18).
Lee JS et al., studied the differences of corneal morphological parameters in DM patients compared with age matched, healthy control subjects (18). The diabetic subjects had greater CCT, reduced ECD and hexagonality, and more CV of the corneal endothelium than the control. Lee JS et al., found thicker corneas with the mean CCT significantly higher in diabetic (588±272.7 μ μ m) than in the control group (567±873.8 μ μ m) (p-value <0.05) and more irregular cell sizes with the mean value of CV which was significantly higher in diabetics (38.2±0.4) than in the control group (35.4±0.6) (p-value <0.05), as in present study (19). Lee JS et al., demonstrated significantly less mean ECD in diabetics (2577±2727.3 cell/mm2) than in the control group (2699.9738.7 cell/mm2) (p-value <0.05) and significantly higher mean value of hexagonality for diabetics than for normal persons (p-value <0.05) (19).
Inoue K et al., documented a significant reduction in ECD of diabetic corneas (2493±330 cells/mm2) compared to controls (2599±278 cells/mm2) (p-value=0.016) (20). The CV in cell area was significantly higher in the diabetic group (37.2±6.0) than in the control group (35.4±5.0). There was no significant difference between the percentages of hexagonal cells and CCT in the diabetic group (56.1±8.5% and 538±36 μ, respectively) and the control group, (56.7±6.3% and 537±38 μ, respectively). The present study, found reduction in ECD of diabetic corneas (2493±330 cells/mm2) compared to controls, but statistically insignificant (p-value=0.821) along with significant results in CV (p-value=0.034) as this study. This study also concluded significant difference in terms of CCT (p-value=<0.001) and insignificant difference in terms of HEX % (p-value=0.718) between diabetic and control group.
In 1999, Roszkowska AM et al., evaluated 23 type 2 DM patients for CCT, ECD, CV and HEX% (13). They found significant difference in reduction of the mean ECD of 5% in type 2 DM patients. Roszkowska AM et al., found that the CCT was significantly higher with p-value <0.05 in the type 2 DM group (13). Present study also demonstrated the significant difference in the CCT in type 2 DM patients in comparison to control subjects (p-value=<0.001)
In another study done by Claramonte PJ et al., on 953 non diabetic patients and 47 diabetic patients concluded that diabetic cornea were thicker (mean CCT=571.96±26.81 μ μ m) when compared with non diabetic patients (544.89±35.36 μ μ m) with p-value <0.001) (21). This results were in concordance with present study findings.
Su DH et al., the Singapore Malay eye study, examined the correlation of diabetes with central CCT in 3239 Malay adults (22). They found significantly thicker diabetes cornea than in those without diabetes (547.2 μm vs 539.3 μm, p-value<0.001). In comparison to this present study, sample size was very small but end results were similar.
Choo M et al., evaluated CCT, ECD, CV and HEX% of 200 eyes of type II diabetics and 100 eyes of non diabetic control patients (23). They reported significant increase CV (67.2±47.2% vs 58.2±43.0%, p-value <0.01) in diabetic group which is in concordance with present study findings. They also found reduced ECD (2541.6±516.4 vs 2660.1±515.5 cells/mm2, p-value <0.01) and hexagonality (41.1%±19.6% vs 45.2%±20.6%, p-value <0.01). They also reported no significant difference in CCT (μm; 517.3±53.4 vs 510.8±71.9, p-value=0.149).
In a study done on Indian population (1191 type 2 DM patients and 121 controls) by Sudhir RR et al., observed no difference in the mean CCT, hexagonality (%), and CV of cell among cases and controls (11). In contrast to this, in our Indian study population, we observed significant difference in the mean CCT and CV. Sudhir RR et al., showed lower mean ECD (cells/mm2) in cases than in controls (2550.96 vs 2634.44; p-value=0.001) which is dissimilar to our study (11).
Storr-Paulsen A et al., conducted a prospective clinical study on 107 type 2 DM patients and 128 non diabetic patients to compare ECD, CV, HEX%, CCT (1). In their study they concluded that Type II diabetic subjects did not differ from the non diabetic control subjects with regards to ECD (2578 vs 2605 cells/mm2), HEX%, or CV, but showed significant increase in CCT (538 versus 546 μ), (p-value <0.05). Present study also concluded significant difference with regard to CCT but also to CV.
In another study done by Stella B et al., to assess ECD and CCT in 125 diabetic patients with 90 controls (24). The mean ECD (2511±252 cells/mm2) and mean CCT (539.7±33.6 μ μ m) varied significantly from those the control group ECD (2713±132 cells/mm2) (p-value <0.0001), CCT (525.0±45.3 μ μ ) (p-value=0.003). With regards to CCT, present study also found diabetic cornea significantly thicker than control but ECD difference did not differ significantly though it was lower in diabetic cornea.
A study was in done in 2017 with CCT, ECD, CV and percentage of hexagonal cells of 57 patients (57 eyes) with DM2 and 45 controls (45 eyes). In this study it was found that ECD was significantly lower in the diabetic cornea (2,491.98±261.08 cell/mm2) than in control group (2,629.68±293.45 cell/mm2) (p-value=0.014). CV was higher in diabetic cornea (0.41±0.07) (p-value=0.008). The diabetic cornea group (33.24%±10.25%) had lower percentage of hexagonal cells than the control group (34.24%±8.73%), but the difference was not statistically significant (p-value=0.603). Also, diabetic cornea (545.61±30.39 μ μ m) was thicker than control group (539.42±29.22 μ μ m), but not statistically significant (p-value=0.301) (15). In contrast to this study, in present study, statistically significant thicker diabetic cornea, was found than control group (p-value <0.001) and ECD values were found lower and HEX% were found higher in diabetic group but without significant difference (p-value=0. 821 and p-value 0.985, respectively). In terms of CV, both studies found higher levels in diabetic cornea with statistically significant different from controls cornea.
Comparison between corneal parameters and duration of diabetes patients: In present study, no correlation was found between CCT, ECD, CV and HEX% values with the duration of diabetes. Comparison of the CCT (total eyes) between the two groups shows that CCT, is higher in >10 years group, ECD is higher in <10 years group, CV is higher in >10 years group, HEX% is higher in>10 years group.
On reviewing the literature, it was found that many authors and researchers concluded the same and didn’t find any association between duration of disease and changes in CCT, ECD, CV and HEX%.
Inoue K et al., performed multivariate regression analysis to assess duration of type 2 DM relation to ECD that indicated that duration of type 2 DM was not significantly correlated with the ECD (20).
Choo M et al., performed Pearson correlation analysis that showed that duration of diabetes had no significant correlations with CCT, CV, hexagonality or ECD (23). El-Agamy and Alsubaie S also observed insignificant difference for the same (15). In their study, eyes with DM duration of ≤10 years had higher ECD (p-value=0.658), and more hexagonality than those with DM duration of >10 year (p-value=0.111). Also, they found insignificant differences in CCT (p-value=0.431) and CV (p-value=0.927) between the two groups.
Contrary to present study and other studies mention above, Lee JS et al., found CCT significantly higher for >10 years (595.9±4.2 μm) duration of diabetes than for diabetes of ≤10 years (582.2±3.7μm) (p<0.05) (19).
One of the recent study done by Stella B et al., demonstrated significant reduction of ECD by about 32 cell/mm2 for diabetics with duration of >10 years when compared with those with duration of ≤10 years (p-value <0.05) (24). They also found thicker cornea for diabetics with duration of >10 years (p-value >0.05).
Comparison of corneal parameters according to HbA1c: In present study, no significant correlation was found between CCT and CV with the level of HbA1c. Comparison of the CCT between the two groups showed that CCT, ECD, CV, were higher in >7% group, HEX% was higher in ≤7% group. After going deep through the literature, it was concluded that only few of the studies stated correlation between HbA1c levels and changes in CCT, ECD, CV and HEX. Contrary to present study, Larsson L et al., demonstrated no correlation between the HbA1c and CCT, ECD, CV and HEX% in type 2 DM group (18). Similarly, Inoue K et al., performed multivariate regression analysis to assess HbA1c value relation to ECD that indicated that HbA1c was not significantly correlated with the EC (20). Su DH et al., the Singapore Malay Eye Study found thicker cornea in diabetic patients having higher HbA1C levels (p-value <0.001) (22). Storr-Paulsen A et al., carried out multivariate analysis that revealed lower ECD with higher HbA1c values (p-value <0.05) in diabetic group (1). But CCT, CV and HEX% were not associated with HbA1c levels. In the diabetic group, lower cell counts were associated with higher HbA1c values (p-value <0.05). These findings are not accordance with present study result.
Yazgan S et al., also found significant difference in CCT between group HbA1c ≤7% and group HbA1c >7% (p-value <0.001) (25). El-Agamy and Alsubaie S, in their study showed diabetic patients with HbA1c% ≤7.5 had higher, but not statistically significant, ECD (2,537.62±311.86 cell/mm2) than those with HbA1c% >7.5 (2,458.78±216.06 cell/mm2) (p-value=0.293) and higher hexagonality (5.58%±10.09%) than the other group (31.54%±10.17%) (p-value=0.144) (15). The mean of CV was significantly lower (p-value=0.017) in diabetic patients with HbA1c % ≤7.5 (0.39±0.05) than in the other group (0.43±0.07). Also, there was no statistically significant difference in CCT between the two groups (p-value=0.789).
Comparison of corneal parameters with grading of DR: In present study, DR was found in 48 eyes out of which 40 eyes having NPDR and 8 eyes having PDR. The one-way ANOVA test was applied to compare among all three groups and statistical significant difference was found with CCT, CV and hexagonality but not with ECD. Values of CCT and CV among NPDR eyes were higher than PDR eyes; it may be because of number of eyes as these numbers were higher in NPDR than PDR cases. Same reason could explain hexagonality on higher side in PDR eyes than NPDR eyes. Likewise ECD values were found to be higher in eyes with PDR than NPDR eyes but this difference was statistically insignificant. Larsson L et al., studied 60 known patients of DM2 and they found the degree of retinopathy was not significantly correlated with any of the corneal parameters (CCT, ECD, CCT and HEX%) (18). Similarly, Inoue K et al., performed multivariate regression analysis to assess grade of DR value relation to ECD that indicated that grade of DR was not significantly correlated with the ECD (20). Lee JS et al., measured CCT of diabetic patients with normal fundus and background DR and found higher CCT values in patients with DM compared with control group (19). Roszkowska AM et al., reported thickened central corneas and altered endothelial morphology in diabetic patients with background retinopathy compared with normal healthy subjects (13).
In addition to above mentioned studies, El-Agamy A and Alsubaie S, found no significant differences between CCT, ECD, CV, and hexagonality percentage in diabetic patients without DR, with NPDR, and with PDR (p-value=0.344, 0.806, 0.284, and 0.500, respectively) (15). Results of this study provide a great insight into role of preoperative evaluation of corneal morphology in diabetic population, undergoing cataract surgery, glaucoma surgery, corneal transplantation surgery, pan retinal photocoagulation of diabetic retina. Increased blood sugar level in diabetes reduces the activity of sodium-potassium adenosine triphosphatase (Na-K-ATPase) of the endothelium and causes morphological and structural changes in cornea.
Limitation(s)
In present study, patients who had history of laser photocoagulation for DR were excluded due to its influence on the corneal structures. Diabetic patients who had intravitreal injections of antivascular endothelial growth factor therapy given were not included in this study. This exclusion produced a small sample size, so additional studies with increased number of subjects are required to substantiate the results. Another limitation of the study includes not taking into account possible confounding factors like smoking and corneal diameter.
This study documented that type 2 DM resulted in a reduction of ECD and increased CV along with slightly increased in hexagonality. There was higher CV in the diabetic group. There was a correlation between the changes in corneal parameters like ECD, CV, HEX%, CCT with the duration of DM and severity of DR and glycaemic control {glycosylated haemoglobin (HbA1c) level}. Results of this study suggest that long lasting DM may warrant a corneal endothelium evaluation along with CCT before any intraocular surgery. Thicker central cornea associated with DM should be taken into consideration while obtaining accurate intraocular pressure measurements in diabetic population.
DOI: 10.7860/JCDR/2022/59987.17387
Date of Submission: Sep 01, 2022
Date of Peer Review: Sep 26, 2022
Date of Acceptance: Dec 10, 2022
Date of Publishing: Feb 01, 2023
AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. NA
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