|Year : 2020 | Volume
| Issue : 1 | Page : 4-10
Tear film assessment in sudanese diabetic patients attending Jabir Abu Eliz Diabetic Center, Khartoum, Sudan
Saeeda Mohammed Osman, Mahgoub Saleem
Department of Ophthalmology, Faculty of Medicine, Al-Neelain University, Khartoum, Sudan
|Date of Submission||06-Jul-2020|
|Date of Acceptance||10-Jul-2020|
|Date of Web Publication||31-Dec-2020|
Prof. Mahgoub Saleem
Department of Ophthalmology, Faculty of Medicine, Al-Neelain University, P.O. Box: 10139, Khartoum 11111
Background: Several local and systemic conditions predispose the eye to the development of dry eye disorders due to tear film dysfunction, which is presented in variable degrees of eye irritations and inflammation. Diabetes mellitus (DM) is among the most common risk factors of dry eye disease (DED). It is more common in older females than males. Tear film assessment can be tested with some simple tests such as Schirmer's test (ST), fluorescein strip (FS) (breakup time [BUT]) test, and lissamine green strip (LGS) test.
Objective: The aim of this study is to assess the tear film dysfunction in diabetic patients with ST, FS papers, and LGS papers and compare their diagnostic values.
Materials and Methods: In a cross-sectional hospital-based study, consecutive 126 diabetic patients were examined at Jabir Abu Eliz Diabetic Center in Khartoum for their tear film dysfunction. All selected patients had simultaneously undergone ST, FS (BUT) test, and LGS test in the same order and equal definite intervals in all patients over a 2-month period (September 1, 2013–November 1, 2013). Clinical and personal information was obtained by direct patients and chart review before complete ophthalmic examinations.
Results: The mean age of the study group was 53 ± 12.1 years (30–78 years). Fifty-seven patients (45.2%) were female and 69 (54.8%) were male. In the age group, 11 (8.7%) patients were of type I DM, whereas 115 (91.3%) of type II DM. Forty-four (34.9%) patients had good DM control and 82 (65.1%) had poor DM control. The ST results of the current study demonstrated the presence of 142 patients (56.3%) in the “normal Schirmer's grade,” 49 patients (19.4%) in “mild-to-moderate Schirmer's grade,” and 61 patients (24.2%) in “severe Schirmer's grade.” In the BUT “FS” test, 165 patients (65.5%) gave normal results, whereas 87 patients (34.5%) showed severe tear dysfunction results, with a highly significant difference with P = 0.001. Whereas, in the LGS test, 201 patients (79.8%) were of “normal grade” results and 51 patients (20.2%) were “mild-to-moderate” grade.
Conclusion: DED is an important feature of poorly controlled DM, which can be easily detected by performing a variety of simple quick tests such as the ST, fluorescein tear BUT test, and LGS test. There is notable variation among these three tears; therefore, a combination of any two tests is necessary. There is a strong correlation between qualities of the DM control, duration of DM, and severity of DED.
Keywords: Dry eye syndrome, fluorescein strip papers, Jabir Abu Eliz Diabetic Center, lissamine green, Schirmer's test, tear film dysfunction
|How to cite this article:|
Osman SM, Saleem M. Tear film assessment in sudanese diabetic patients attending Jabir Abu Eliz Diabetic Center, Khartoum, Sudan. Albasar Int J Ophthalmol 2020;7:4-10
|How to cite this URL:|
Osman SM, Saleem M. Tear film assessment in sudanese diabetic patients attending Jabir Abu Eliz Diabetic Center, Khartoum, Sudan. Albasar Int J Ophthalmol [serial online] 2020 [cited 2021 Jun 16];7:4-10. Available from: https://www.bijojournal.org/text.asp?2020/7/1/4/305763
| Introduction|| |
Dry eye disease (DED) is defined by the International Dry Eye WorkShop (2007) as a multifactorial disease of tears and ocular surface that may result in symptoms of discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. It is a common global clinical disorder which tends to affect up to 35% of normal adults among the general population., The prevalence of DED in community-based studies was found to be lower than in hospital-based studies. The prevalence of DED in diabetics may exceed 50%.,, Since diabetic patients, especially with poor metabolic control, were more likely to present with DED due to their decreased tear film stability, dry eye tests should be added to the routine screening of diabetes. Females may report a high incidence of DED than males. There is a progressive decline in tear production in older adults due to age-related changes in the lacrimal gland., Tear film assessment can be tested with some simple tests which can be done in the clinics, such as Schirmer's test (ST), fluorescein strip (FS) (breakup time ([BUT]) test, and lissamine green strip (LGS) test: (1) ST: Clinically, it is the most common with well-defined “Schirmer scores.” Schirmer I measures total tear secretion: basal and reflex. Schirmer II measures only the reflex and not the basal secretion. The use of topical anesthetic with the test is very controversial. (2) FS: It is also known as “tear film BUT test (BUT or TF-BUT)” performed using FSs under the cobalt blue filter on slit lamp, BUT; the test was considered to be “positive for dry eyes” if the BUT was <10 s. (3) LGS: LGS is an “epithelial staining” dye like the Rose Bengal (RB) but causes no pain, discomfort, or corneal toxicity that is associated with RB. The LGSs were placed into the lower fornix to stain the cornea blue by causing blue corneal speckling (dot formation) under very low slit-lamp illumination with white light., LGS test recommended grades as normal, mild, moderate, and pathological at minimum of 4 points to be adopted., LG dye is indirectly ascertaining the presence of reduced tear volume by the detection of damaged epithelial cells, as LG dye is taken up by the dead or dying cells of the corneal epithelium. It is less sensitive and more transient, and very difficult to be appreciated on slit lamp,, so advisable to be done in a combination of another test as FS.
| Materials and Methods|| |
In a hospital-based cross-sectional descriptive study, consecutive 126 patients (252 eyes) referred to the Department of Ophthalmology at Jabir Abu Eliz Diabetic Center (JDC), with a diagnosis of type I or type II diabetes mellitus (DM), were included in this study. Tear film assessment was tested with ST, FS (BUT) test, and LGS test. All selected patients had simultaneously undergone the three tests: ST, FS (BUT) test, and LGS test in the same order and equal definite intervals in all patients. The study was done over 2-month period (September 1, 2013–November 1, 2013). Clinical and personal information was obtained by direct patients and chart review before complete ophthalmic examinations. Exclusion criteria were determined by the presence of ocular or systemic pathologies that are lead to dry eye syndrome (DES) including idiopathic, contact lenses, trauma, eye surgeries, collagen vascular diseases, and drugs.
The same identical structured methods of the following three tests (ST, FS (BUT) test, and LGS test) were done for each eye and each participant in the whole study group, as “one eye at a time.”
The Schirmer's test (ST) was done with 'TearFlo' Schirmer paper strips (manufactured by: HUB Pharmaceuticals, LLC (USA). 100); 6617 N Scottsdale Road, Suite 204, Scottsdale, AZ 85250 [email protected]); the test was done “one eye at a time” without topical anesthesia, after reassuring the patients. The eyes were gently dried of excess tears from the inferior fornix with filter or tissue papers. Then, the folded end was inserted at the junction of the middle and outer thirds of the lower lid taking care not to touch the cornea or lashes, and the patient was asked to keep the eyes gently closed. After 5 min, the filter paper was to be removed and the amount of wetting was measured from the folded region. The reading of “less than 10 mm” of the wetting portion after 5 min without anesthesia was to be considered as “a positive ST.” We adopted the grading of Kanski and Bowling, in which the ST was distributed in three grades: normal for more than 10 mm, mild to moderate between 6 and 10 mm, and severe for <5 mm (positive ST for dry eye wetting of the paper after 5 min.
Fluorescein strips (breakup time)
TF-BUT test (BUT) measurement was performed using FSs by (Fluorets®, Chauvin Pharmaceuticals Ltd., Surrey, UK). The FS was introduced gently in the lower fornix, in the lower conjunctival sac, “one eye at a time.” Then, the patient was asked to blink several times and then to keep the eyes open. Corneas were examined under cobalt blue filter on slit lamp (Haag-Streit Diagnostics-Slit Lamp BQ 900/870 18./2014 – 11; Haag-Streit AG Gartenstadtstrasse 10 3098 Koeniz, Switzerland, www.haagstreit.com), whereas the dry areas were indicated by the presence of a black spot. The time between the last blink and the appearance of a random dry spot was recorded in seconds by stopwatch as BUT. There are scaling grades in the BUT. A positive test for dry eyes was taken when BUT was <10 s, as the normal time for tear film breakup is 15–20 sA.
Lissamine green strips
Tear production was measured by LGS dye-impregnated paper strips (Green Glo™ lissamine green [LG] in 10 sterile strip packs). The LGSs were wetted with drops of sterile saline and then placed into the lower fornix, in the conjunctival sac with minimal stimulation of the eye, “one eye at a time and for 1 min.” Patients were asked to blink gently to allow adequate corneal and conjunctival staining. Blue corneal speckling (dot formation) to detect dry patches as well as any muco-deficient or damaged cells was detected under very low illumination with white light of the slit lamp. In the LGS test, we adopted the recommended LG grades: normal for Grade 0–1 and mild to moderate for Grades 2–6, which was to be read on the cornea and palpebral conjunctiva (nasal and temporal palpebral conjunctiva): 1 point for few spots, 2 points for several separate spots, and 3 points for conflurative spots. A maximum of 9 points can be reached. The test is pathological at minimum 4 points.
Ethical approval was obtained from the Ministry of Health. Informed consent was obtained from each patient, and they were reassured that their data will be kept in confidentiality.
| Results|| |
Tear film dysfunction was assessed in 126 diabetic patients (252 eyes) at JDC, Khartoum. The mean age of the study group was 53 ± 12.1 years (30–78 years). Sixty-nine patients (54.8%) were male and 57 (45.2%) were female [Figure 1] and [Table 1].
In the distribution of patient's groups, there were 7 patients (5.6%) below 30 years of age (6 women [4.8%] and 1 man [0.8%]), there were 41 patients (32.5%) in the age group of 30–50 years (23 females [18.3%] and 18 males [14.3%]), and there were 78 patients (61.9%) in the >50 years' age group (28 females [22.2%] and 50 males [39.7%]) [Figure 2] and [Table 1].
|Figure 2: Distribution of sex according to age group. Note: <: less than; >: more than|
Click here to view
The majority of the study population were of DM II (115; 91.3%), whereas only 11 patients were of DM I (8.7%) [Figure 3]. Regarding the distribution of diabetes type according to age group, 7 (5.6%) patients in the age group below 30 years were of DM I and no DM II, whereas in the 30–50 years' age group, 4 patients (3.2%) of DM I and 37 patients (29.4%) of DM II. All the 78 (62%) patients in the age group >50 years were of DM II [Figure 4] and [Table 2].
|Figure 3: Distribution of diabetes type (DM I-DM II). Note: DM type I/type II: Diabetes mellitus type 1 and 2|
Click here to view
|Figure 4: Distribution of diabetes type according to age groups (DM I-DM II). Note: DM type I/type II: Diabetes mellitus type 1 and 2; <: less than|
Click here to view
|Table 2: Distribution of the type of diabetes according to age group (diabetes mellitus I-diabetes mellitus II)|
Click here to view
In the current study, there was a correlation between qualities of the DM control and the duration of DM. Those with good control with their DM duration <5 years were 18 patients (14.3%), and 21 patients (16.7%) had poor DM control. Those with good control with their DM duration <5 years were 18 patients (14.3%), and 21 patients (16.7%) had poor DM control. While in those with their DM duration between 5-10; 8 (6.4%) of them had good DM control and 19 (15.1%) had poor DM control. On the other hand; patients who were more than 10 year's DM duration; 18 (14.3%) of them had good DM control and 42 (33.3%) had poor DM control. Therefore, in this study group, almost the number of patients with poor DM control (82, 65.1%) was double that of those with good control (44, 34.9%) [Table 3].
|Table 3: Correlation between diabetes mellitus control and diabetes mellitus duration|
Click here to view
In the current study, the basal and reflex tear function measured by the ST revealed that 142 eyes of 71 patients scored normal tear production of 56.3% in the “normal Schirmer's grade.” The total “abnormal tear production” detected by the same ST scored 43.7% (19.1 as mild to moderate + 24.6% as severe), which means that there was a significant reduction in the basal and reflex tear secretion among the currently studied diabetics (43.7%) [Table 4]. This ST abnormal tear production score was lower than BUT scores and higher than LGSs [Figure 5] and [Figure 6].
|Figure 5: Comparison of the “three tear film test” parameters among the study groups|
Click here to view
|Figure 6: [Figure 6] Variations in Normal and Abnormal Tear production between the 3 tests (ST, BUT, LGS) Notes: ST: Schirmers Test (ST); BUT: Tear Film Break Up Time (BUT)LDS: Lissamine Green Strips (LGS) (P≤0.001)|
Click here to view
|Table 4: Data analysis of the “three tear film test” parameters among the study groups|
Click here to view
The TF-BUT test (BUT) results in 164 eyes of 82 patients [Table 4] were very deferent from the other two tests, as the BUT normal tear production was 34.9%, being the lowest normal scores when compared by ST and LGS results [Figure 5] and [Figure 6]. In the meantime, the abnormal tear production of BUT (only as severe, no mild-to-moderate grade) scored almost double (65.1%) that of the normal tear production of the same “BUT” test, showing severe tear dysfunction result, with a highly significant difference with P = 0.001. Hence, BUT seems to detect DED better than the other two tests.
The LGS test (LGS) results in 200 eyes of 100 patients [Table 4] scored the highest normal tear production (79.4%) and the lowest abnormal (only as mild-to-moderate grade, no severe) tear production (20.6%) [Figure 5]. LGS seems to be the least in detecting DED as compared with ST and BUT [Figure 5] and [Figure 6].
The results of the three tear production tests show highly significant differences between them (P = 0.001). In general, the average reading of the normal tear production of the three tests was 56.9% and the average of the abnormal tear production of the three tests was 43.1% in a ratio of almost 3:2 [Figure 7].
|Figure 7: Average normal and abnormal tear productions of the three tests (ST, BUT, and LGS). Note: ST: Schirmer's test; BUT: Tear film breakup time; LGS: Lissamine green strip; Normal TP: Average normal tear production; Abnormal TP: Average abnormal tear production|
Click here to view
| Discussion|| |
DED (DES) is a common disorder of tear film due to tear deficiency or excessive tear evaporation. This leads to the damage of the interpalpebral ocular surface, which causes distressing sore eyes symptoms., Early diagnosis and timely treatment are essential to avoid serious complications secondary to inevitable microbial corneal infection and ulceration. Diabetic patients suffer tear dysfunction more than nondiabetics because of their variable degrees of peripheral corneal neuropathy. This serious ocular surface disorder could be confirmed by performing a variety of simple quick tear film production tests, especially for diabetic patients., It is advisable in diabetics, even without subjective symptoms of dry eye to do multiple tear film tests, to assess the exact degree of the diabetic DES, as some tests have more diagnostic values in certain patients than others. There is no one test that can assess the ocular tear film alone, as each test with others can give satisfactory results. Impression cytology can be the ideal method, but it is a long invasive process that required laboratory help.,
In the current study, the ST results revealed that 43.7% of the current diabetic patients scored a significant “positive ST,” which indicates a significant reduction in basal and reflex tear secretion among these diabetics. In another way, 43.7% of these diabetics with “positive ST,” and they have an “abnormal tear production” or tear film dysfunction, so they are possible candidates for full-blown DED. The current study results were in alignment with the result obtained by Saito and colleagues (Korea; 2003)  who revealed that the basal and reflex tear secretion was significantly reduced. Also, Martin Geobbels in University Eye Hospital of Bonn, Germany (2000)  demonstrated that the majority of diabetics; specially insulin dependent, showed distinct signs of conjunctival surface disease due to reduced tear secretion.
In the present work, BUT was significantly reduced; 65.1% had “positive test” for tear dysfunction and only 34.9% had normal tear function (normal >10 min). This study was agreed with many other international studies in deferent places like West China Hospital study by Yu et al. in a multitest study, including BUT, ST, epithelial staining tests, and others which concluded that tear film dysfunction was high in diabetic patients. Idu and Oghre from the University of Benin (2010) reported “abnormal tear production” detected by the ST and BUT tests, especially with poorly controlled type II diabetics (DM II); however, it was not statistically significant (P > 0.05). Dogru et al. from Japan (2001) had the same impressions and results. Ozemir et al. in Turkey (2003) attributed the ocular surface disorders and tear dysfunction in patients with type 2 diabetes to poor metabolic control and severity of proliferative diabetic retinopathy.
Hence, the positive results of reduced tear film stability in the current study were supported by the above international similar studies. All of them reported positive results that indicate decreased tear production in diabetics, especially with long duration, poor metabolic control, and severe microvascular complications (proliferative diabetic retinopathy). Misra et al. in New Zealand National Eye Centre suggest that ocular surface abnormalities may occur in parallel with diabetic peripheral neuropathy as tear film stability was inversely associated with total body neuropathy score.
LG vital stain (LG) test in the present study demonstrated a very unusual low “positive” results as compared with the ST and BUT tests; it was 4 times less (20.2%) than the result of normal tear's function (79.8%). As far as we searched the literature, no similar result was found. Even though, a lot of explanations may support this LG low positive results: Some researchers like Najafi et al. (Tehran, Iran, 2015) commented about the less accuracy of LG staining as compared with the other tear's function tests (ST and BUT). Delaveris et al. in Sydney, Australia, demonstrated significant differences in LG staining intensity from different companies; staining was significantly higher with some LG brands and lower in others that may underestimate the presence of DED. These variations may be one of the causes of this study “very unusual low positive results.”
LG demonstrates conjunctival staining rather than corneal staining, but the ocular surface staining is commonly employed as an outcome measurement of corneal and conjunctival staining, according to Oxford Scheme for grading ocular surface staining in dry eye conditions. Therefore, the ocular surface area in LG staining will be less than the actual ocular surface area needed for final results. Ramsey suggested that, in an article published in April 2011 in the journal of “Review of Cornea and Contact lenses,” the use of these vital stains in practice should be in combination rather than alone, for example, LG + FS. Bunya et al. (2012–2016) developed semi-automated quantification of LG test of the bulbar conjunctiva from digital images but still not for a commercial use. This new technology may improve the quality of LG score for tear production assessment in the future.
| Conclusion|| |
Tear film dysfunction and ]DED is an important feature of poorly controlled DM, which can be easily detected by performing a variety of simple quick tests such as the ST, fluorescein tear BUT test, and LGS test. BUT test demonstrated the highest sensitivity in detecting the tear dysfunction, whereas LGS test produces the lowest positive tear production and seems to be the least in detecting DED as compared with fluorescein test and BUT. There is notable variation among the three tear production diagnostic tests (ST, BUT test, and LGS test). Therefore, the best test is a combination of any two tests. There is a strong correlation between qualities of the DM control, duration of DM, and severity of tear film dysfunction.
A detailed ocular surface evaluation is recommended for all diabetic patients to detect early evidence of ocular surface disorders, DED, as prompt treatment prevents future vision-threatening complications. BUT test demonstrated a high sensitivity as compared to other tests, and it should be used as an initial screening tool in outpatient departments to detect early tear film instability in diabetics. The best test results can be obtained by combination at least two tests including BUT.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
The definition and classification of dry eye disease: Report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf 2007;5:75-92.
Nebbioso M, Del Regno P, Gharbiya M, Sacchetti M, Plateroti R, Lambiase A. Analysis of the pathogenic factors and management of dry eye in ocular surface disorders. Int J Mol Sci 2017;18:1764.
Chia EM, Mitchell P, Rochtchina E, Lee AJ, Maroun R, Wang JJ. Prevalence and associations of dry eye syndrome in an older population: The Blue Mountains Eye Study. Clin Exp Ophthalmol 2003;31:229-32.
Zou X, Lu L, Xu Y, Zhu J, He J, Zhang B, et al
. Prevalence and clinical characteristics of dry eye disease in community-based type 2 diabetic patients: The Beixinjing eye study. BMC Ophthalmol 2018;18:117.
Burda N, Mema V, Md EM, Selimi B, Zhugli S, Lenajni L, Bunjaku I. Prevalence of dry eye syndrome at patients with Diabetes Mellitus tip 2, one year retrospective study May 2011 June 2012. J Acute Dis December 2012;1:110–114. DOI:10.1016/S2221-6189(13)60026-8.
Zhang X, Zhao L, Deng S, Sun X, Wang N. Dry eye syndrome in patients with diabetes mellitus: Prevalence, etiology, and clinical characteristics. J Ophthalmol 2016;2016:8201053.
Moss SE, Klein R, Klein BE. Prevalence of and risk factors for dry eye syndrome. Arch Ophthalmol 2000;118:1264-8.
Saeed HA, Tufaili HA. Tear film instability in diabetic patients. Karbala J Med 2018;11:3918-3922.
Moss SE, Klein R, Klein BE. Long-term incidence of dry eye in an older population. Optom Vis Sci 2008;85:668-74.
Patel R, Zhu M, Robertson DM. Shifting the IGF-axis: An age-related decline in human tear IGF-1 correlates with clinical signs of dry eye. Growth Horm IGF Res 2018;40:69-73.
Galor A, Feuer W, Lee DJ, Florez H, Venincasa VD, Perez VL. Ocular surface parameters in older male veterans. Invest Ophthalmol Vis Sci 2013;54:1426-33.
Senchyna M, Wax MB. Quantitative assessment of tear production: A review of methods and utility in dry eye drug discovery. J Ocul Biol Dis Infor 2008;1:1-6.
Li N, Deng XG, He MF. Comparison of the 'Schirmer1' test with and without topical anesthesia for diagnosing dry eye. Int J Ophthalmol 2012;5:478-81.
Rahman A, Fasih U, Huda WU, Shaikh A, Yahya K. Comparison of Schirmers test and tear film breakup time test to detect tear film abnormalities in patients with Pterygium. J Pak Med Assoc 2012;62:1214-6.
Eom Y, Lee JS, Keun Lee H, Myung Kim H, Suk Song J. Comparison of conjunctival staining between lissamine green and yellow filtered fluorescein sodium. Can J Ophthalmol 2015;50:273-7. doi: 10.1016/j.jcjo.2015.05.007. PMID: 26257220.
Foulks GN. Challenges and pitfalls in clinical trials of treatments for dry eye. Ocul Surf 2003;1:20-30.
McCulley J. Dry Eye Patterns with Lissamine Green. ASCRS Eye World; 2008.
Singh S. A Comparative Clinical Study of Ocular Surface Disorders in Diabetic and Non-Diabetic Persons. Master's Degree in Ophthalmology; Department of Ophthalmology; M.S. Ramaiah Medical College, Bangalore-560007. Rajiv Gandhi University of Health Sciences; Karnataka, Bangalore. Available from: http://www.rguhs.ac.in/cdc/onlinecdc/uploads/01_M010_43536.doc
[Last Accessed on 2019 oct 01].
Methodologies to Diagnose and Monitor Dry Eye Disease: Report of the Diagnostic Methodology Subcommittee of the international dry eye workshop. Ocular Surface 2007;5:108-52.
Phadatare SP, Momin M, Nighojkar P, Askarkar S, Singh KK. A comprehensive review on dry eye disease: Diagnosis, medical management, recent developments, and future challenges. Adv Pharma 2015;2015:704946.
Kanski JJ, Bowling B. Clinical Ophthalmology: A Systematic Approach, capture 4. Dry Eye Disorders. 7th ed. Edinburgh; New York: Elsevier Inc.; Saunders, 2011.
Klein BE, Klein R. Lifestyle exposures and eye diseases in adults. Am J Ophthalmol 2007;144:961-9.
Gulati A, Sullivan R, Buring JE, Sullivan DA, Dana R, Schaumberg DA. Validation and repeatability of a short questionnaire for dry eye syndrome. Am J Ophthalmol 2006;142:125-31.
Midena E, Brugin E, Ghirlando A, Sommavilla M, Avogaro A. Corneal diabetic neuropathy: A confocal microscopy study. J Refract Surg 2006;22:S1047-52.
Rahman A, Yahya K, Ahmed T, Sharif-Ul-Hasan K. Diagnostic value of tear films tests in type 2 diabetes. J Pak Med Assoc 2007;57:577-81.
Figueroa-Ortiz LC, Jiménez Rodríguez JE, García-Ben A, García-Campos J. Study of tear function and the conjunctival surface in diabetic patients. Arch 2011;86:107-12.
Al Wadani FA, Nambiar R, Abdul Wahhab KM, Al Asbali T, Nambiar A, Rahaman AU. Reliability and utility of impression cytology in the diagnosis of dry eye. Niger J Ophthalmol 2016;24:51-6.
Mathers WD. Why the eye becomes dry: A cornea and lacrimal gland feedback model. CLAO J 2000;26:159-65.
Saito J, Enoki M, Hara M, Morishige N, Chikama T, Nishida T. Correlation of corneal sensation, but not of basal or reflex tear secretion, with the stage of diabetic retinopathy. Cornea 2003;22:15-8.
Geobbels M. Tear secretion and tear film function in insulin dependent diabetes. Br J Ophthalmol 2000;84:19-21.
Yu L, Chen X, Qin G, Xie H, Lv P. Tear film function in type 2 diabetic patients with retinopathy. Ophthalmologica 2008;222:284-91.
Idu FK, Oghre E. Tear secretion and tear film stability in Nigerians with non-insulin dependent diabetes mellitus. South Afr Optom 2010;69:140-5.
Dogru M, Katakami C, Inoue M. Tear function and ocular surface change in noninsulin dependent diabetes mellitus. Ophthalmology 2001;108:586-92.
Ozemir M, Buyukbese MA, Cetinkaya A, Ozemir G, Risk factors for ocular surface disorder in patients with diabetes mellitus. Diabetes Res Clin Pract 2003;59:195-9.
Misra SL, Patel DV, McGhee CN, Pradhan M, Kilfoyle D, Braatvedt GD, et al
. Peripheral neuropathy and tear film dysfunction in type 1 diabetes mellitus. J Diabetes Res 2014;2014:848659.
Najafi L, Malek M, Valojerdi AE, Khamseh ME, Aghaei H. Dry eye disease in type 2 diabetes mellitus; comparison of the tear osmolarity test with other common diagnostic tests: A diagnostic accuracy study using STARD standard. J Diabetes Metab Disord 2015;14:39.
Delaveris A, Stahl U, Madigan M, Jalbert I. Comparative performance of lissamine green stains. Cont Lens Anterior Eye 2018;41:23-7.
Bron AJ, Evans VE, Smith JA. Grading of corneal and conjunctival staining in the context of other dry eye tests. Cornea 2003;22:640-50.
Ramsey AC. Vital Stains: What You Really Need to Know. RCCL; 2011.
Bunya VY, Chen M, Zheng Y, Massaro-Giordano M, Gee J, Daniel E, et al
. Development and evaluation of semiautomated quantification of lissamine green staining of the bulbar conjunctiva from digital images. JAMA Ophthalmol 2017;135:1078-85.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
[Table 1], [Table 2], [Table 3], [Table 4]