How Diabetes Impacts the Cornea and Ocular Surface

Corneal compromise can interfere with IOL power calculation, delay wound healing and exacerbate dry eye.

By Onsiri Thanathanee, MD and Terrence P. O'Brien, MD

Diabetes patients experience higher rates of corneal and ocular surface abnormalities. These can affect the cataract surgeon's approach to surgery as well as postoperative management. Below we will review some of the most pressing concerns of note to anterior segment surgeons.

Tear film abnormalities. Ocular surface disease is one of several important problems to consider in diabetic patients with cataract, especially dry eye with a dysfunctional tear state. Several studies have demonstrated significantly higher prevalence and incidence of dry eye in diabetic patients in comparison with healthy individuals.^1-3 Corneal sensitivity and tear function tests were both decreased.^4,5

Additionally, there is a correlation between the severity of dry eye and the degree of diabetic retinopathy.^6,7 Proliferative diabetic retinopathy patients tend to have more severe tear film dysfunction than nonproliferative diabetic retinopathy patients, as assessed by tear break-up time and Schirmer testing.^6,7 The possible mechanisms contributing to tear dysfunction are diabetic neuropathy and/or vascular changes in the lacrimal gland.^1,5

Cataract surgery can also worsen the tear film function and exacerbate the severity of dry eye disease.^8,9 Topical anesthetics and other preservative-containing eye drops used in cataract surgery may add to an already compromised and relatively neurotrophic cornea in diabetic patients. The surgical incisional location and shape are also related. There is a worsening of dry eye tests among cases employing a grooved cataract incision type compared with a single-plane incision. However, there were no significant differences in tear function observed between superior and temporal incisional locations.¹⁰

Both preoperative and postoperative dry eye disease are well established in studies of diabetic patients and can initiate postoperative ocular surface problems such as recurrent corneal erosion syndrome, persistent epithelial defect, delayed wound healing and corneal scar/opacity. Careful preoperative ocular surface examination and aggressive treatment before surgery may alleviate signs and symptoms, including complications of postoperative dry eye disease in diabetic patients undergoing cataract surgery.

Furthermore, tear film instability can interfere with ocular biometry and intraocular lens power calculations. The keratometer mires from an irregular ocular surface are usually distorted and can interfere in reliable measurements resulting in an error of IOL power determination.¹¹

Corneal concerns. Some layers of the cornea (epithelium, basal epithelium, sub-basal nerve plexus and endothelium) have been found to be abnormal in diabetic patients. The corneal epithelial abnormalities in diabetic patients have been reported in both human and animal models.^12-14 In a diabetic rat model of wound healing, the corneal epithelial wound closure was delayed and the phenotype of epithelium was changed.¹³ In addition, abnormal changes of epithelium in diabetic patients after cataract surgery were noted with increased average cell area and decreased hemidesmosomes.^12,15

This phenomenon may play a role in delay of normal wound healing after cataract surgery and predispose patients to possible intraocular infection. A number of studies have reported that diabetic patients are more prone to develop postoperative endophthalmitis and also tend to have poorer visual outcome after treatment for endophthalmitis.^16-19

Chang et al.²⁰ investigated basal epithelial density and sub-basal nerve branch density in healthy control patients compared with nondiabetic (NDR), nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) patients. The results showed significant decrease of basal epithelium cell density among NPDR and PDR groups compared with the control group with no significant correlation with duration of diabetes or HbA1c.

Corneal nerve density was also decreased in NDR, NPDR and PDR. Moreover, the correlation between corneal nerve change together with basal cell density and severity of diabetic retinopathy was observed. This may explain the corneal complications after cataract surgery in diabetic patients, particularly in those cataract patients with severe forms of diabetic retinopathy.

Abnormalities of the corneal endothelium were also observed before and after cataract surgery^21-23 even though one prior study showed no significant difference.²⁴ In the preoperative period, there is a tendency for diabetic patients to have a thicker cornea with more pleomorphism and polymegathism, though the trend was not statistically significant.²¹ Also, the corneal thickness and endothelial cell loss were significantly higher in the diabetic group compared with the nondiabetic group at one month and one week after surgery, respectively.²² The thicker corneas in diabetic patients not only exhibit indirect endothelial dysfunction but also implicate an error of intraocular pressure measurement.²³ Therefore, complete preoperative corneal evaluation and meticulously conducted surgical procedures with generous use of ophthalmic viscoelastic devices may alleviate postoperative complications.

Iris/pupil issues. With respect to pupil abnormality in diabetic patients undergoing cataract surgery, inadequate dilation has been observed.²⁵ The possible mechanism is autonomic neuropathy.^26,27 Furthermore, constriction of the pupil during cataract surgery in a diabetic patient is more obvious than in non-diabetic controls.²⁸ However, there has been no study that has determined the correlation between degree of miosis and severity of disease.

Floppy iris syndrome — which is comprised of undulation of the iris in response to fluid currents, repeated prolapsed of iris and progressive constriction of pupil — can be found intraoperatively in diabetic patients. Even though some of its clinical manifestation are similar to autonomic neuropathy of the diabetic iris, most studies found no association between floppy iris syndrome and diabetes.^29-31 Consequently, the poor pupillary dilation may cause insufficient visualization during surgery and then generate potential operative complications.

Use of topically administered nonsteroidal anti-inflammatory drugs before and after cataract surgery has been reported to reduce complications.^32-34 The benefits of topical NSAIDs are prevention of intraoperative miosis during cataract surgery in diabetic patients, prevention and treatment of cystoid macular edema following cataract surgery and decreased postoperative inflammation. For higher-risk diabetic patients, one to two weeks of preoperative and four to six weeks of postoperative topical NSAIDs instillation is recommended to prevent CME after cataract surgery.³² Preoperative recognition and careful preoperative topical medication administration may lessen the risk of pupil-associated complications in diabetic patients undergoing cataract surgery.

IOL considerations. Careful intraocular lens selection is essential to improve the postoperative visual outcome in diabetic patients. Silicone IOLs can lead to a larger area of posterior capsule opacification after cataract surgery in diabetic patients compared with acrylic IOLs. However, higher anterior chamber flare reaction in the acrylic IOLs group was found in the early postoperative period.³⁵

Multifocal IOLs have been more commonly used today due to the desire for concomitant presbyopic correction in select patients. However, loss of contrast sensitivity, a potential complication of multifocal IOLs, is accentuated with diabetic retinopathy. Patients with multifocal IOLs implantation experience greater loss of contrast sensitivity compared with monofocal IOLs.³⁶ Diabetic patients may have some ocular complications such as diabetic macular edema, dry eye disease and diabetic retinopathy, which can worsen overall contrast sensitivity. Therefore, multifocal IOL implantation should generally be avoided in most diabetic patients undergoing cataract surgery.

The incidence of posterior capsule opacification is significantly higher in diabetic patients compared with non-diabetic patients following cataract surgery when as demonstrated by the increased requirement for Nd:YAG laser posterior capsulotomy.³⁷ Nevertheless, the stage of diabetic retinopathy and systemic status of diabetes did not correlate with degree of PCO.³⁸

Meticulous attention to removal of all residual cortical material as well as lens epithelial cells is essential to delay the development of PCO and the need for Nd:YAG laser posterior capsulotomy. OM

References

1. 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 Apr;5(2):75-92.
2. Moss SE, Klein R, Klein BE. Prevalence of and risk factors for dry eye syndrome. Arch Ophthalmol 2000 Sep;118(9):1264-8.
3. Moss SE, Klein R, Klein BE. Incidence of dry eye in an older population. Arch Ophthalmol 2004 Mar;122(3):369-73.
4. Yoon KC, Im SK, Seo MS. Changes of tear film and ocular surface in diabetes mellitus. Korean J Ophthalmol 2004 Dec;18(2):168-74.
5. Cousen P, Cackett P, Bennett H, Swa K, Dhillon B. Tear production and corneal sensitivity in diabetes. J Diabetes Complications 2007 Nov-Dec;21(6):371-3.
6. 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 Jan;22(1):15-8.
7. Yu L, Chen X, Qin G, Xie H, Lv P. Tear film function in type 2 diabetic patients with retinopathy. Ophthalmologica 2008;222(4):284-91.
8. Liu X, Gu YS, Xu YS. Changes of tear film and tear secretion after phacoemulsification in diabetic patients. J Zhejiang Univ Sci B 2008 Apr;9(4):324-8.
9. Khanal S, Tomlinson A, Esakowitz L, Bhatt P, Jones D, Nabili S, et al. Changes in corneal sensitivity and tear physiology after phacoemulsification. Ophthalmic Physiol Opt 2008 Mar;28(2):127-34.
10. Cho YK, Kim MS. Dry eye after cataract surgery and associated intraoperative risk factors. Korean J Ophthalmol 2009 Jun;23(2):65-73.
11. Norrby S. Sources of error in intraocular lens power calculation. J Cataract Refract Surg 2008 Mar;34(3):368-76.
12. Tsubota K, Chiba K, Shimazaki J. Corneal epithelium in diabetic patients. Cornea 1991 Mar;10(2):156-60.
13. Wakuta M, Morishige N, Chikama T, Seki K, Nagano T, Nishida T. Delayed wound closure and phenotypic changes in corneal epithelium of the spontaneously diabetic Goto-Kakizaki rat. Invest Ophthalmol Vis Sci 2007 Feb;48(2):590-6.
14. Didenko TN, Smoliakova GP, Sorokin EL, Egorov VV. [Clinical and pathogenetic features of neurotrophic corneal disorders in diabetes]. Vestn Oftalmol 1999 Nov-Dec;115(6):7-11.
15. Tabatabay CA, Bumbacher M, Baumgartner B, Leuenberger PM. Reduced number of hemidesmosomes in the corneal epithelium of diabetics with proliferative vitreoretinopathy. Graefes Arch Clin Exp Ophthalmol 1988;226(4):389-92.
16. Phillips WB, 2nd, Tasman WS. Postoperative endophthalmitis in association with diabetes mellitus. Ophthalmology 1994 Mar;101(3):508-18.
17. Doft BH, Wisniewski SR, Kelsey SF, Fitzgerald SG. Diabetes and postoperative endophthalmitis in the endophthalmitis vitrectomy study. Arch Ophthalmol 2001 May;119(5):650-6.
18. Doft BH, Wisniewski SR, Kelsey SF, et al. Diabetes and postcataract extraction endophthalmitis. Curr Opin Ophthalmol 2002 Jun;13(3):147-51.
19. Khandekar RB, Tirumurthy S, Al-Harby S, Moorthy NS, Amir I. Diabetic retinopathy and ocular co-morbidities among persons with diabetes at Sumail Hospital of Oman. Diabetes Technol Ther 2009 Oct;11(10):675-9.
20. Chang PY, Carrel H, Huang JS, Wang IJ, Hou YC, Chen WL, et al. Decreased density of corneal basal epithelium and subbasal corneal nerve bundle changes in patients with diabetic retinopathy. Am J Ophthalmol 2006 Sep;142(3):488-90.
21. Siribunkum J, Kosrirukvongs P, Singalavanija A. Corneal abnormalities in diabetes. J Med Assoc Thai 2001 Aug;84(8):1075-83.
22. Morikubo S, Takamura Y, Kubo E, Tsuzuki S, Akagi Y. Corneal changes after small-incision cataract surgery in patients with diabetes mellitus. Arch Ophthalmol 2004 Jul;122(7):966-9.
23. Ozdamar Y, Cankaya B, Ozalp S, Acaroglu G, Karakaya J, Ozkan SS. Is There a Correlation Between Diabetes Mellitus and Central Corneal Thickness? J Glaucoma 2009 Dec 30.
24. Wojciechowska R, Bolek S, Janiec S. [Corneal endothelium in patients with diabetes after extracapsular cataract extraction with intraocular lens implantation in the posterior chamber]. Klin Oczna 1995 Jul-Sep;97(7-8):221-2.
25. Yang YB, Yu YB, Fu Q. [The autonomic pupillary dysfunction in type II diabetes mellitus]. Zhonghua Yan Ke Za Zhi 2006 Jul;42(7):616-9.
26. Hreidarsson AB. Pupil size in insulin-dependent diabetes. Relationship to duration, metabolic control, and long-term manifestations. Diabetes 1982 May;31(5 Pt 1):442-8.
27. Smith SA, Smith SE. Evidence for a neuropathic aetiology in the small pupil of diabetes mellitus. Br J Ophthalmol 1983 Feb;67(2):89-93.
28. Zaczek A, Zetterstrom C. Cataract surgery and pupil size in patients with diabetes mellitus. Acta Ophthalmol Scand 1997 Aug;75(4):429-32.
29. Chadha V, Borooah S, Tey A, Styles C, Singh J. Floppy iris behaviour during cataract surgery: associations and variations. Br J Ophthalmol 2007 Jan;91(1):40-2.
30. Neff KD, Sandoval HP, Fernandez de Castro LE, Nowacki AS, Vroman DT, Solomon KD. Factors associated with intraoperative floppy iris syndrome. Ophthalmology 2009 Apr;116(4):658-63.
31. Altan-Yaycioglu R, Gedik S, Pelit A, Akova YA, Akman A. Clinical factors associated with floppy iris signs: a prospective study from two centers. Ophthalmic Surg Lasers Imaging 2009 May-Jun;40(3):232-8.
32. O'Brien TP. Emerging guidelines for use of NSAID therapy to optimize cataract surgery patient care. Curr Med Res Opin 2005 Jul;21(7):1131-7.
33. Papa V, Russo S, Russo P, Di Bella A, Santocono M, Milazzo G. Topical naproxen sodium for inhibition of miosis during cataract surgery. Prospective, randomized clinical trials. Eye (Lond) 2002 May;16(3):292-6.
34. Thaller VT, Kulshrestha MK, Bell K. The effect of pre-operative topical flurbiprofen or diclofenac on pupil dilatation. Eye (Lond) 2000 Aug;14 (Pt 4):642-5.
35. Elgohary MA, Hollick EJ, Bender LE, Heatley CJ, Wren SM, Boyce J, et al. Hydrophobic acrylic and plate-haptic silicone intraocular lens implantation in diabetic patients: pilot randomized clinical trial. J Cataract Refract Surg 2006 Jul;32(7):1188-95.
36. Mesci C, Erbil HH, Olgun A, Aydin N, Candemir B, Akcakaya AA. Differences in contrast sensitivity between monofocal, multifocal and accommodating intraocular lenses: long-term results. Clin Experiment Ophthalmol 2010 Jul 26.
37. Ionides A, Dowler JG, Hykin PG, Rosen PH, Hamilton AM. Posterior capsule opacification following diabetic extracapsular cataract extraction. Eye (Lond)1994;8 (Pt 5):535-7.
38. Hayashi K, Hayashi H, Nakao F, Hayashi F. Posterior capsule opacification after cataract surgery in patients with diabetes mellitus. Am J Ophthalmol 2002 Jul;134(1):10-6.