Diabetic Corneal Disease: Manifestations and Management

Clinicians should look for dry eye and keratopathy in diabetic patients during routine eye examinations.

By Malkit (Mona) Singh, MD, MPA and Bala K. Ambati, MP, PhD, MBA

Diabetic retinopathy is the leading cause of blindness in working-age adults in the United States,1 but diabetes can affect other ocular structures as well, particularly the cornea.2 Diabetic patients experience higher rates of vision-threatening corneal disease than patients without diabetes.3 The disease can trigger acceleration of ocular surface diseases such as dry eye disease (DED) and diabetic keratopathy.4 Delayed wound healing and loss of innervation in this most densely innervated tissue in the body can also cause degeneration of anatomic integrity and function in the cornea and increase the risk of postoperative intraocular infection in diabetic patients.3,5


DED, a condition in which the tear film is abnormal and there are changes in the anterior surface of the cornea, is one of the most common ophthalmic diagnoses among diabetic patients.6 Pathogenic mechanisms in DED include abnormal ocular surface sensitivity, decreased tear production, delayed corneal reepithelialization, increased tear osmolarity, and increased ocular surface inflammation. Risk factors include longer duration of diabetic disease and higher hemoglobin A1c levels.4 Intraocular surgery, such as cataract surgery, can worsen the function of the tear film and exacerbate the severity of DED.3

Common DED tests to assess tear film quality, team film production, and corneal epithelial defects include tear breakup time, Schirmer testing, and fluorescein evaluation, respectively. Diabetic neuropathy leads to lower tear breakup time values due to loss of conjunctival goblet cells, the cells that produce mucin. The mucin layer covers the corneal epithelium and reduces evaporative tear loss.7 Diabetic neuropathy and vascular changes also compromise lacrimal gland function and corneal integrity.8

The changes to the corneal surface that result from DED in diabetes can lead to ocular discomfort, visual disturbance, burning, foreign body sensation, photophobia, and blurred vision.9 Diabetic patients with DED have increased risks of corneal infections, scarring, and, in advanced diabetic disease, corneal perforation and irreversible tissue damage. Corneal complications of DED such as superficial punctate keratitis, neurotrophic keratopathy, and persistent epithelial defects, also occur more frequently in diabetic patients.6

It is important to aggressively treat the ocular surface of diabetic patients with appropriate dry eye therapy. Timely treatment of DED with punctal plugs or artificial tears can reduce the risk of complications and temporarily reduce blurred vision.10 Numerous formulations of artificial tears are available with various combinations of surfactants, viscosity agents, and electrolytes.

Topical antiinflammatory medications, such as corticosteroids, NSAIDs, and cyclosporine ophthalmic emulsion (Restasis; Allergan), can also be used to control the inflammatory effect of DED.11 Long-term use of corticosteroids, however, can increase the risk of bacterial, viral, and fungal infection; elevated intraocular pressure; and cataract formation.12 NSAIDs have less severe side effects.4 Topical cyclosporine increases tear production and the number of conjunctival goblet cells.13


Patients with diabetes can have keratopathies and corneal epithelial erosions that may recur and persist, unresponsive to conventional treatment regimens.4 Diabetic keratopathy can lead to permanent vision loss secondary to persistent epithelial defects and to subsequent scarring, as well as chronic corneal edema. It is a condition that should be prevented, diagnosed early, closely monitored, and treated, particularly before corneal complications occur.14

Corneal abnormalities in diabetes include loss of corneal sensation,15 weakened adhesion between the basement membrane of the corneal epithelium and the corneal stroma (Figure 1),16 and delayed epithelial healing.17 Even minimal trauma can cause corneal abrasions in diabetic patients (Figure 2).16 Therefore, in a patient with diabetes presenting with recurrent corneal erosions, it is likely more beneficial to perform epithelial reinforcement using corneal anterior stromal puncture with a needle, rather than epithelial debridement with diamond burr polishing.

Figure 1. Corneal epithelial defect in a diabetic patient after vitrectomy (A). Phase-contrast photomicrograph demonstrating intact epithelial sheet removed during vitreoretinal surgery because of loose adherence (Paraphenylenediamine, × 400; B) Electron micrograph of basal cell surface from epithelial scraping showing intact basement membrane attached to epithelial cells (× 25,000; C).28

Figure 2: Large central corneal erosion, stained with fluorescein, in a diabetic patient with no history of past or present corneal trauma or previous episode.29

The incidence of diabetic keratopathy is increased after pars plana vitrectomy, penetrating keratoplasty, laser iridectomy, and refractive surgery.18-21 Recurrent corneal erosion syndrome is a particular problem for diabetic patients undergoing vitrectomy because the entire epithelium may be removed at surgery for visualization, followed by delayed healing. Corneal edema is also more common in diabetic patients after vitrectomy.22

Diabetic keratopathy is generally treated with artificial tears and a bandage soft contact lens, tarsorrhaphy, or amniotic membrane graft for reepithelialization and surface protection in patients with ulcerations.23 Prokera (Bio-Tissue), which is amniotic membrane in the form of a contact lens, is a nice option for healing these injured corneas.

In our experience, vitamin C, doxycycline, and medroxyprogesterone 1% drops are helpful in preventing corneal melting in patients with persistent epithelial defects. Albumin 5% drops can help promote reepithelialization. Once the epithelium has healed, judicious use of topical steroids can help to minimize corneal haze. Preservative-free antibiotics such as moxifloxacin are useful adjuncts to prevent infection.

Diabetic patients experience higher rates of corneal and ocular surface abnormalities, which can affect the eye care professional’s approach to preventive care and perioperative management.


The best way to prevent corneal manifestations of diabetes is to monitor and closely regulate blood glucose. Regardless of the duration of diabetic disease, patients with poor metabolic control show increased tear dysfunction and corneal pathology.24 The level of DED and diabetic keratopathy correlates statistically with the level of diabetic retinopathy.25,26 Patients with proliferative diabetic retinopathy tend to have more severe tear film dysfunction and diabetic keratopathy than those with nonproliferative diabetic retinopathy.15,26,27

Clinicians should be aware of DED and keratopathy in diabetic patients during routine eye examinations. Aggressively monitoring and treating corneal diabetic disease, such as DED symptoms and corneal erosion, and maintaining tight glucose control for diabetes overall, are critical steps to prevent worsening morbidity and vision loss. n

1. Centers for Disease Control and Prevention. Common Eye Disorders. 2013. http://www.cdc.gov/visionhealth/basic_information/eye_disorders.htm. Accessed October 15, 2015.

2. Kincaid MC. Pathology of Diabetes Mellitus. In: Duane’s Foundations of Clinical Ophthalmology, vol. 3, Pathology of the Eye. Tasman W, Jaeger EA, eds. Philadelphia: Lippincott Williams & Wilkins; 2006. 3. Thanathanee O, O’Brien TP. How diabetes impacts the cornea and ocular surface. Ophthalmology Management. November 2010.

4. Sayin N, Kara N, Pekel G. Ocular complications of diabetes mellitus. World J Diabetes. 2015;6(1):92-108.

5. Rosenberg M, Tervo TM, Immonen IJ, et al. Corneal structure and sensitivity in type 1 diabetes mellitus. Invest Ophthalmol Vis Sci. 2000;41(10):2915-2921.

6. Seifart U, Strempel I. The dry eye and diabetes mellitus. Ophthalmologe. 1994;91:235-239.

7. Dogru M, Katakami C, Inoue M. Tear function and ocular surface changes in noninsulin-dependent diabetes mellitus. Ophthalmology. 2001;108(3):586-592.

8. Cousen P, Cackett P, Bennett H, et al. Tear production and corneal sensitivity in diabetes. J Diabetes Complications. 2007;21(6):371-373.

9. [no authors listed]. 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(2):75-92.

10. Albietz JM, Bruce AS. The conjunctival epithelium in dry eye subtypes: effect of preserved and non-preserved topical treatments. Curr Eye Res. 2001;22:8-18.

11. Pflugfelder SC. Anti-inflammatory therapy of dry eye. Ocul Surf. 2003;1:31-36.

12. Yang CQ, Sun W, Gu YS. A clinical study of the efficacy of topical corticosteroids on dry eye. J Zhejiang Univ Sci B. 2006;7:675-678.

13. Zhou XQ, Wei RL. Topical cyclosporine A in the treatment of dry eye: a systematic review and meta-analysis. Cornea. 2014;33:760-767.

14. Cisarik-Fredenburg P. Discoveries in research on diabetic keratopathy. Optometry. 2001;2(11):691-704.

15. Saito J, Enoki M, Hara M, et al. Correlation of corneal sensation, but not of basal or reflex tear secretion, with the stage of diabetic retinopathy. Cornea. 2003;22:15-18.

16. Azar DT, Spurr-Michaud SJ, Tisdale AS, et al. Altered epithelial-basement membrane interactions in diabetic corneas. Arch Ophthalmol. 1992;110(4):537-540.

17. McDermott AM, Xiao TL, Kern TS, Murphy CJ. Non-enzymatic glycation in corneas from normal and diabetic donors and its effects on epithelial cell attachment in vitro. Optometry. 2003;74:443-452.

18. Chung H, Tolentino FI, Cajita VN, et al. Reevaluation of corneal complications after closed vitrectomy. Arch Ophthalmol. 1988;106:916-919.

19. Chou L, Cohen EJ, Laibson PR, Rapuano CJ. Factors associated with epithelial defects after penetrating keratoplasty. Ophthalmic Surg. 1994;25:700-703.

20. Jeng S, Lee JS, Huang SC. Corneal decompensation after argon laser iridectomy--a delayed complication. Ophthalmic Surg. 1991;22:565-569.

21. Simpson RG, Moshirfar M, Edmonds JN, Christiansen SM. Laser in-situ keratomileusis in patients with diabetes mellitus: a review of the literature. Clin Ophthalmol. 2012;6:1665-1674.

22. Kinoshita JH. Aldose reductase in the diabetic eye: XLIII Edward Jackson Memorial Lecture. Am J Ophthalmol. 1986;102(6):685-692.

23. Abdelkader H, Patel DV, McGhee CNj, Alany RG. New therapeutic approaches in the treatment of diabetic keratopathy: a review. Clin Experiment Ophthalmol. 2011;39:259-270.

24. Ozdemir M, Buyukbese MA, Cetinkaya A, Ozdemir G. Risk factors for ocular surface disorders in patients with diabetes mellitus. Diabetes Res Clin Pract. 2003;59(3):195-199.

25. Nepp J, Abela C, Polzer I, et al. Is there a correlation between the severity of diabetic retinopathy and keratoconjunctivitis sicca? Cornea. 2000;19(4):487-491.

26. Hyndiuk RA, Kazarian EL, Schultz RO, et al. Neurotrophic corneal ulcers in diabetes mellitus. Arch Ophthalmol. 1977;95(12):2193-2196.

27. Yu L, Chen X, Qin G, Xie H, Lv P. Tear film function in type 2 diabetic patients with retinopathy. Ophthalmologica. 2008;222(4):284-291.

28. Mora ML, Smith RE. Chapter 15, Corneal and Systemic Diseases, Figure 31. Duane’s Clinical Ophthalmology, Volume 4, External Diseases. 2006. http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v4/ch015/031f.html Accessed October 19, 2015.

29. EyeRounds Online Atlas of Ophthalmology, Ophthalmic Atlas Images by EyeRounds.org, The University of Ioma, licensed under Creative Commons Attribution. Figure: Corneal erosion. http://webeye.ophth.uiowa.edu/eyeforum/atlas/pages/corneal-erosion-OS.html. Accessed October 21, 2015.

Section Editor Bala K. Ambati, MD, PhD, MBA
• Professor of ophthalmology, John A. Moran Eye Center, University of Utah, Salt Lake City
• Director of cornea research, John A. Moran Eye Center, University of Utah, Salt Lake City
• Financial disclosure: none acknowledged

Malkit (Mona) Singh, MD, MPA
• Postdoctoral research fellow, John A. Moran Eye Center, University of Utah, Salt Lake City
• Financial interest: none acknowledged