Transcript Diabetic Eye Disease

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
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No general agreement on whether there 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 HgbA1c 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, ptosis, 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
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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.
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 (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.