Diabetic Eye Disease

1
Diabetic Eye Disease

• Not Just Retinopathy

2
Eye Anatomy
3
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

4
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

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Cornea
6
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

7
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.

8
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 (plt 0.01).
• The most frequent complications occurring in the
  diabetic population are punctate epithelial
  erosions and persistent epithelial defects.

9
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

10
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

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Cornea normal cell morphology
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Cornea Diabetic Patient
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Cornea Resolution of Edema After Cataract
Surgery
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Cornea Endothelial Cell Loss After Cataract
Surgery
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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

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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.

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Neovascular Glaucoma
18
Neovascular glaucoma
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Neovascular Glaucoma
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Angle Closure Glaucoma

• End result of neovascular glaucoma
• Can also be caused or exacerbated by lens
  swelling during periods of hyperglycemia lens
  induced glaucoma

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Lens Induced Glaucoma
22
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

23
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

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Cataract
25
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

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Cortical Cataract
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Cortical Cataract
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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

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Posterior Subcapsular Cataract
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Posterior Subcapsular Cataract
31
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

32
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

33
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

34
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 NdYAG laser capsulotomy

35
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

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Cataract Surgery Complications Cystoid Macular
Edema
Normal Macula
Cystoid Macular Edema
Optical Coherence Tomography
37
Cataract Surgery Complications Cystoid Macular
Edema
38
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

39
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

40
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

41
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

42
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

43
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
44
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

45
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

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Central Retinal Vein Occlusion
47
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

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Diabetic Papillopathy
49
Diabetic Papillopathy
50
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

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Non-Arteritic Anterior Ischemic Optic Neuropathy
52
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

53
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

54
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)

55
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

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Mucormycosis
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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

58
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