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 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 non-
diabetics
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 VAs
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 co-
morbid 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
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