Diabetic Eye Disease Not Just Retinopathy Eye Anatomy

Diabetic Eye Disease Not Just Retinopathy

Eye Anatomy

Lids, Lashes and Conjunctiva • Diabetics have an increased incidence of styes, chronic blepharitis, and bacterial conjunctivitis • More likely to be colonized by bacteria such as Staphylococcus Aureous and Staphylococcus Epidermidis that commonly cause these disorders • Can lead to scarring of lid margins and exposure keratopathy • Especially dangerous after surgery because can seed internal eye and cause endophthalmitis

Cornea • Function – refraction, protection, “window” • Must be transparent – achieved with uniform structure, avascularity and deturgescence • Corneal fluid balance maintained by active bicarbonate pump in endothelium and by barrier function of endothelium and epithelium

Cornea

Cornea • Diabetics have decreased corneal sensitivity • Decreased nerve fiber density seen microscopically • Predisposes to neurotrophic ulcers and difficulties with contact lenses • Early in course of disease some studies report corneal thickening (likely due to edema) • Late corneal thinning with associated increase risk in erosion

Cornea • Increased incidence of bacterial keratitis in diabetes, especially uncontrolled DM • Corneal ulcers due to Moraxella liquefaciens more common in diabetics and alcoholics – deep penetration and prolonged, difficult treatment • Diabetics more prone to recurrent corneal erosions and to slow healing of corneal wounds • Epithelial basement membrane in diabetic eyes is poorly adherent to stroma, in part due to decreased numbers of hemidesmosomes, leading to sloughing of entire layer when traumatized.

Cornea • Diabetics tend to have more problems with contact lenses – should they have LASIK or PRK? • Photorefractive Keratectomy (PRK) is problematic because it involves removal of the epithelium which is slower to heal in diabetic patients • Laser In Situ Keratomileusis (LASIK) is better in that respect because it involves making a flap and applying the laser directly to the stroma; however trauma is still done to epithelium • A study done in Oregon showed that diabetic eyes treated with LASIK had an overall complication rate of 47% compared with the control population complication incidence of 6. 9% (p< 0. 01). – The most frequent complications occurring in the diabetic population are punctate epithelial erosions and persistent epithelial defects.

Cornea • Corneal edema develops during periods of relative hypoxia (including during contact lens wear) or when endothelium is damaged • Diabetic corneas do not recover from edema as quickly as normal corneas • Conflicting evidence regarding cause of decreased regulation of fluid balance – Enzymatic dysfunction of bicarb pump – Protein glycosylation within cornea – Involvement of aldose reductase with build-up of sorbitol in corneal stroma – Endothelial cell loss and fragility leading to impaired barrier function

Cornea • Any type of intraocular surgery results in some degree of corneal edema, thought to be due to mechanical stress on the endothelium with resulting decreased barrier function • Although diabetics appear to have normal number and density of endothelial cells, they often have irregular morphology and have prolonged recovery periods after surgery due to persistent corneal edema and endothelial cell loss

Cornea – normal cell morphology

Cornea – Diabetic Patient

Cornea – Resolution of Edema After Cataract Surgery

Cornea – Endothelial Cell Loss After Cataract Surgery

Primary Open Angle Glaucoma • • • No general agreement on whethere is an increased rate of primary open-angle glaucoma in diabetics Largely due to inconsistent definitions of both DM and glaucoma and to study exclusions or sampling bias 1994 Beaver Dam Eye Study – Diabetics (mostly type II) had incidence of glaucoma 4. 2% vs 2. 0% in participants without DM. When people treated for glaucoma included, rates were 7. 8% in diabetics compared with 3. 9% in those without diabetes. DM and POAG well defined and standardized 1995 Baltimore Eye Survey – Diabetics no more likely to have POAG than non-diabetics. DM defined by history only. Authors suggest reported increase prevalence due to more screening in diabetics (previously diagnosed POAG associated with DM) 1996 Rotterdam Study – Newly diagnosed diabetics had increased prevalence of high tension POAG. Glaucoma dx based on visual field defects 2002 Ocular Hypertension Treatment Study – Showed protective effect of DM on POAG. Excluded patients with diabetic retinopathy. DM defined by history only

Neovascular Glaucoma • Begins when ischemic retinal tissue releases VEGF into the ocular fluid resulting in stimulation of new vessel formation in the iris or anterior angle (known as rubeosis iridis) • Over time, a fibrovascular membrane forms, covering the iris and growing into the angle to inhibit aqueous outflow • Eventually this membrane contracts and anterior synechiae develop occluding the angle completely.

Neovascular Glaucoma

Neovascular glaucoma

Neovascular Glaucoma

Angle Closure Glaucoma • End result of neovascular glaucoma • Can also be caused or exacerbated by lens swelling during periods of hyperglycemia “lens induced glaucoma”

Lens Induced Glaucoma

Lens • Fluctuating myopia occurs when excess glucose in aqueous fluid diffuses into the lens. • Some of the glucose is reduced by aldose reductase to sorbitol, which accumulates in the lens drawing free water in with it • When the body rapidly changes from a hyperglycemic to a hypoglycemic state, sorbitol, which is less permeable and harder to metabolize, will remain in the lens longer. The difference in osmotic pressure results in the influx of water from the aqueous humor into the lens, causing lenticular swelling • Glycosylation of lens proteins also occurs causing irregularity in previously uniform structure and thus decreasing transparency • Causes change in index of refraction within different components of the lens • Also causes change in curvature of lens, affecting refraction • Can rarely result in lens-induced glaucoma

Lens - Cataracts • Diabetics 2 to 4 times more likely to develop cataracts than non-diabetics • Patients with DM develop cataracts earlier in life than non-diabetics • Risk increased with poor diabetic control as manifest by high Hgb. A 1 c or kidney disease and with increased age and/or duration of disease • May be partly due to glycosylation of lens proteins

Cataract

Lens - Cataract • Cortical cataract – most common type in elderly (diabetics and non-diabetics) • May occur 20 to 30 years earlier in patients with DM • Special type of cortical cataract seen in young people with uncontrolled insulin dependent DM called a “snowflake” cataract – Rapid progression with total opacification in just a few weeks – Also has subcapsular opacities – not seen as much now because of better DM control

Cortical Cataract

Cortical Cataract

Lens - Cataract • Diabetics much more likely to get posterior subcapsular cataract (OR about 3) • PSCs appear to be caused by a dysplastic change in germinal epithelium resulting in vacuolation

Posterior Subcapsular Cataract

Posterior Subcapsular Cataract

Cataract Surgery • Indications are the same as for nondiabetics • Also indicated for monitoring of diabetic retinopathy when lens opacity prevents visualization of fundus • Increased rates of perioperative and postoperative complications, especially in presence of diabetic retinopathy

Cataract Surgery • Due to co-morbidities related to diabetes such as coronary artery disease and renal insufficiency, these patients have higher rates of perioperative morbidity (still generally very safe surgery) • However, there has recently been an emphasis on earlier cataract extraction in diabetics so some of the relative risks are offset by younger age at surgery

Cataract Surgery – Anterior Segment Complications • Most significant anterior segment complication of cataract surgery is development or progression of neovascularization of the iris or angle, leading to glaucoma • Removal of cataract allows easier pathway for VEGF produced by ischemic retina to reach anterior chamber and promote neovascularization • Risk lower when diabetic retinopathy has been treated with laser photocoagulation therapy • Preservation of posterior lens capsule common in phacoemulsification surgical technique does not appear to provide any extra protection against neovascularization in anterior chamber

Cataract Surgery – Anterior Segment Complications • Pupillary block (by lens), posterior synechiae, severe iritis, and pigment precipitation on the IOL are all more common in diabetic patients • Prolonged period of corneal edema after surgery and more damage done to corneal endothelial cells • Posterior capsule opacification occurs more frequently and sooner postoperatively in diabetics, requiring Nd: YAG laser capsulotomy

Cataract Surgery – Posterior Segment Complications • Diabetic retinopathy and macular edema frequently occur or worsen after cataract surgery • Other sight threatening complications such as vitreous or suprachoroidal hemorrhage or tractional retinal detachment happen more frequently in patients with diabetes • Post-surgical complication rates and visual outcomes in diabetics depend on several factors – Most important predictor of outcome is preoperative severity of retinopathy and presence or absence of macular edema – Also important: age, gender, insulin treatment, glycemic control, prior laser photocoagulation, prior vitrectomy

Cataract Surgery Complications – Cystoid Macular Edema Normal Macula Cystoid Macular Edema Optical Coherence Tomography

Cataract Surgery Complications – Cystoid Macular Edema

Cataract Surgery - Outcomes • Pre-op no/mild retinopathy – post-op visual acuities similar to non-diabetics (85% VA 20/40 or better); however: – cystoid macular edema after surgery much more prevalent in diabetics – Retinopathy progresses in 15% of pts within 18 months after surgery

Cataract Surgery - Outcomes • Pre-op moderate nonproliferative diabetic retinopathy without macular edema – Higher incidence of progression of retinopathy and incidence of macular edema • Early Treatment Diabetic Retinopathy Study: 12 month VA’s for all eyes with mild to moderate NPDR: only 53% better than 20/40 but 90% better than 20/100 • Benson et al showed development of clinically significant macular edema in 50% of these pts • In some cases progression of DR and ME cause VA to be worse than preoperatively

Cataract Surgery - Outcomes • Pre-op NPDR with macular edema – Poor visual prognosis even with pre-op photocoagulation – Progression of retinopathy in 30% of eyes – Worsening of ME to point of requiring laser in 50% of eyes – Only 50% have post-op improvement in VA – Only 40% have post-op VA of 20/40 or better

Cataract Surgery - Outcomes • Pre-op proliferative diabetic retinopathy – Outcome depends greatly on whether PDR is active vs quiescent and whether macular edema is present preoperatively – When possible, panretinal photocoagulation done preoperatively – With quiescent PDR and no ME, 60% had VA 20/40 or better – With quiescent PDR and ME, only 10% had VA 20/40 or better – With active PDR, very few have VA 20/40 or better unless simultaneous vitrectomy and endolaser PRP performed (still less than 30%) – Other complications of cataract surgery much more prevalent in pts with PDR such as: • 50% of pts with active PDR will have anterior fibrinous uveitis • 6 -9% of pts with PDR will develop neovascularization of the iris or angle

Cataract Surgery • Given the inverse association between the level of retinopathy and visual outcome, it may be better to perform cataract extraction in diabetic patients during earlier stages of retinopathy • However, may cause progression of retinopathy or occurrence of macular edema in previously mild cases so should not be done unless necessary

Cataract Surgery - Outcomes Distribution of visual acuity before and 1 year after lens extraction for all eyes, stratified by the severity of retinopathy before lens extraction - ETDRS

Ciliary Body • Ciliary body used to change shape of lens in order to accommodate • In diabetes, increased glucose in aqueous is deposited in ciliary body, decreasing mobility and thus accomodation • Results in early presbyopia in diabetics

Retinal Vein Occlusion • Diabetics, especially type II, at higher risk for central retinal vein occlusion • Must be distinguished from diabetic retinopathy because treatment differs • CRVO also lead to retinal ischemia and neovascularization

Central Retinal Vein Occlusion

Optic Nerve - Diabetic Papillopathy § Acute optic disc edema typically associated with mild visual loss (20/50 or better) § Most common theory is that it represents a mild form of non-arteritic ischemic optic neuropathy, with reversible ischemia of both the prelaminar and inner surface layers of the optic nerve head § Visual field defects may include increased blind spot, arcuate scotoma or altitudinal scotoma § FA shows diffuse leakage on disc § Bilateral in 50% of cases § More common in type I diabetics (70% of cases) § Good visual prognosis, most younger pts recover to 20/30 or better § Optic disc swelling usually resolves within 2 -10 months with residual mild optic atrophy § Must be differentiated from papilledema and from anterior ischemic optic neuropathy

Diabetic Papillopathy

Diabetic Papillopathy

Optic Nerve – Non-Arteritic Anterior Ischemic Optic Neuropathy • Sudden onset, non-progressive monocular visual loss, usually in elderly patients, often noticed upon waking • Swollen optic nerve, RAPD, dyschromatopsia, inferior altitudinal visual field defect • Occurs 2. 7 to 5 times more commonly in diabetics than non-diabetics, especially with comorbid hypertension • Usually a fixed deficit

Non-Arteritic Anterior Ischemic Optic Neuropathy

Optic Nerve - Superior Segmental Optic Nerve Hypoplasia • Children born to mothers with Type 1 DM may have superior segmental optic nerve hypoplasia • Often asymptomatic with inferior visual field defects or have long history of tripping or running into things at their feet • Rates as high as 8. 8% of children of Type I diabetics have been reported in small studies • Pathogenesis unknown

Oculomotor Nerves • Diabetics are more likely than non-diabetics to have isolated or multiple oculomotor nerve palsies • In a large study of 2229 pts with oculomotor nerve palsy, 13. 7% had known diabetes – 50% involved CN 6, 43% CN 3, and 7% CN 4 – Multiple nerves involved in 2. 6% of pts simultaneously and 3. 9% of pts consecutively – Prevalence of DR lower in pts with palsy than in diabetic controls matched for disease duration • Can be presenting sign of diabetes, rare in pts under 45 yrs old • Ischemic injury to nerve causing demyelination • Third nerve ischemic palsy usually spares pupil because vessel is in center of nerve bundle and pupillary fibers run on exterior surface with alternate blood supply • Usually resolves spontaneously in 3 -4 months

Infection - Endophthalmitis • Several studies have shown increased risk of post-operative endophthalmitis in diabetics • Not surprising since diabetics have been shown to have impaired cellular and humoral immunity as well as delayed wound healing after surgery • May also be because diabetics often have more complicated surgeries and longer operative time (although this was controlled for in some trials)

Infection - Mucormycosis • Over 50% of mucor cases occur in diabetics, especially in pts with ketoacidosis • Usually originates in sinuses • Complete internal and external ophthalmoplegia, decreased vision, proptosis, chemosis, black eschars and discharge • Vascular invasion and tissue necrosis • Mortality over 50%

Mucormycosis

Take Home Messages • Diabetics, especially Type I patients, are at increased risks for many types of ocular disease • Tight glucose control can significantly reduce the incidence of disease and the number of complications associated with treatment • Diabetics should see an ophthalmologist early and often

Bibliography • • • Reifler DM. Neovascular glaucoma after intracapsular and extracapsular cataract extraction in diabetic patients. American Journal of Ophthalmology. 101(3): 386 -8, 1986 Mar 15. Garcia CA. Ruiz RS. Diabetes and the eye. Clinical Symposia. 36(4): 2 -32, 1984. Olsen T. Busted N. Corneal thickness in eyes with diabetic and nondiabetic neovascularisation. British Journal of Ophthalmology. 65(10): 691 -3, 1981 Oct. Negi A. Vernon SA. An overview of the eye in diabetes. Journal of the Royal Society of Medicine. 96(6): 266 -72, 2003 Jun. Nemesure B. Wu SY. Hennis A. Leske MC. Barbados Eye Study Group. Corneal thickness and intraocular pressure in the Barbados eye studies. Archives of Ophthalmology. 121(2): 240 -4, 2003 Feb. Langwinska-Wosko E. Chociszewska-Nitka A. Zielinska E. Hapunik A. [Evaluation of corneal endothelium following cataract surgery in diabetic patients]. Klinika Oczna. 106(1 -2): 28 -30, 2004. Murphy PJ. Patel S. Kong N. Ryder RE. Marshall J. Noninvasive assessment of corneal sensitivity in young and elderly diabetic and nondiabetic subjects. Investigative Ophthalmology & Visual Science. 45(6): 1737 -42, 2004 Jun. Mc. Dermott 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 (St. Louis, Mo. ). 74(7): 443 -52, 2003 Jul. Costin JA. Is laser vision correction safe in patients with diabetes? . Cleveland Clinic Journal of Medicine. 68(5): 385, 2001 May. O'Donnell C. Efron N. Boulton AJ. A prospective study of contact lens wear in diabetes mellitus. Ophthalmic & Physiological Optics. 21(2): 127 -38, 2001 Mar. Morikubo S. Takamura Y. Kubo E. Tsuzuki S. Akagi Y. Corneal changes after small-incision cataract surgery in patients with diabetes mellitus. Archives of Ophthalmology. 122(7): 966 -9, 2004 Jul. Jacobson DM. Vierkant RA. Belongia EA. Nonarteritic anterior ischemic optic neuropathy. A case-control study of potential risk factors. Archives of Ophthalmology. 115(11): 1403 -7, 1997 Nov.

Bibliography • • • Harding JJ. Egerton M. van Heyningen R. Harding RS. Diabetes, glaucoma, sex, and cataract: analysis of combined data from two case control studies. British Journal of Ophthalmology. 77(1): 2 -6, 1993 Jan. Xia X. Zhang X. Xia H. A study of factors related to the incidence of cataract in patients with non-insulin dependent diabetes mellitus. Yen Ko Hsueh Pao [Eye Science]. 17(3): 180 -2, 2001 Sep. Hayashi K. Hayashi H. Nakao F. Hayashi F. Posterior capsule opacification after cataract surgery in patients with diabetes mellitus. American Journal of Ophthalmology. 134(1): 10 -6, 2002 Jul. Squirrell D. Bhola R. Bush J. Winder S. Talbot JF. A prospective, case controlled study of the natural history of diabetic retinopathy and maculopathy after uncomplicated phacoemulsification cataract surgery in patients with type 2 diabetes. British Journal of Ophthalmology. 86(5): 565 -71, 2002 May. Hennis A. Wu SY. Nemesure B. Leske MC. Barbados Eye Studies Group. Risk factors for incident cortical and posterior subcapsular lens opacities in the Barbados Eye Studies. Archives of Ophthalmology. 122(4): 525 -30, 2004 Apr. Hayreh SS. Joos KM. Podhajsky PA. Long CR. Systemic diseases associated with nonarteritic anterior ischemic optic neuropathy. American Journal of Ophthalmology. 118(6): 766 -80, 1994 Dec 15. Patel SV. Mutyala S. Leske DA. Hodge DO. Holmes JM. Incidence, associations, and evaluation of sixth nerve palsy using a population-based method. Ophthalmology. 111(2): 369 -75, 2004 Feb. Trigler L. Siatkowski RM. Oster AS. Feuer WJ. Betts CL. Glaser JS. Schatz NJ. Farris BK. Flynn HW. Retinopathy in patients with diabetic ophthalmoplegia. Ophthalmology. 110(8): 1545 -50, 2003 Aug. Flynn HW, Smiddy WE. Diabetes and Ocular Disease: Past, Present and Future Therapies. Foundation of the American Academy of Ophthalmology Monographs. China 2000. Lazzaroni F. Laffi GL. Galuppi V. Scorolli L. [Paralysis of oculomotor nerves in diabetes mellitus. A retrospective study of 44 cases]. Revue Neurologique. 149(10): 571 -3, 1993. Jacques PF. Moeller SM. Hankinson SE. Chylack LT Jr. Rogers G. Tung W. Wolfe JK. Willett WC. Taylor A. Weight status, abdominal adiposity, diabetes, and early age-related lens opacities.