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Progression of Wet and Dry Age-Related Macular Degeneration (AMD) Following Cataract Surgery: Making Sense of the Current Literature Susan B. Bressler MD Julia G. Levy, PhD Professor of Ophthalmology Johns Hopkins University School of Medicine. Financial Disclosures. Grant Support:

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slide1
Progression of Wet and Dry

Age-Related Macular Degeneration (AMD) Following Cataract Surgery: Making Sense of the Current Literature

Susan B. Bressler MD

Julia G. Levy, PhD Professor of Ophthalmology

Johns Hopkins University School of Medicine

financial disclosures
Financial Disclosures
  • Grant Support:
    • Bausch & Lomb, Genentech, Novartis, Notal Vision, Lumenis, Thrombogenics, Bayer
  • Consultant
    • GlaxoSmithKline
prevalence of amd and cataract
Prevalence of AMD and Cataract
  • Cataract is the leading cause of blindness globally

~1.5 million surgeries/yr in U.S.

  • AMD has been the leading cause of blindness among Americans ≥65 years old

~8 million Americans at risk of advanced AMD

  • Both are age related: anticipate large number of people will have both conditions
reasons to consider cataract surgery in people with amd
Reasons to Consider Cataract Surgery in People with AMD

Surgery may improve visual acuity and quality of life, and:

  • Improve clinical exam diagnostic capabilities
  • Improve quality of images (FAs/OCTs)
  • Improve confidence in appropriateness of treatment recommendations
  • Improve confidence regarding re-treatment recommendations
why worry about cataract surgery accelerating amd development or progression
Why worry about cataract surgery accelerating AMD development or progression?

Light Exposure Theories

  • Animal models exist demonstrating light toxicity and retinal damage, particularly from low wavelength blue light
  • Concern that removal of the crystalline lens permits blue light to reach the macula, accelerating maculopathy
why worry about cataract surgery accelerating amd development or progression1
Why worry about cataract surgery accelerating AMD development or progression?

Inflammation Theories

  • Acute or chronic inflammation induced by cataract surgery may accelerate AMD since inflammation may play a role in development of both non-neovascular and neovascular AMD
    • i.e. macrophage induction of angiogenesis or proinflammatory chemokines may have angiogenic properties
observational data from population studies assessing relationship of amd and cataract surgery
Observational Data from Population Studies Assessing Relationship of AMD and Cataract Surgery
strengths and weaknesses population based studies
Strengths and WeaknessesPopulation Based Studies
  • Strengths:
    • population based
    • standardized measures of assessing lens and AMD status
    • Longitudinal data up to 20 years

Beaver Dam

Blue Mountain

Salisbury Eye Evaluation

Baltimore Eye Survey

Proyecto VER

strengths and weaknesses population based studies1
Strengths and WeaknessesPopulation Based Studies
  • Weaknesses:
    • Findings have been inconsistent within (types of AMD) and between studies
    • No studies have used angiography to define late AMD Small numbers of late AMD cases leads to unstable measures of association
    • Selective survival and loss to follow-up may affect results
    • Association does not imply causation
    • Shared risk factors for AMD and cataract that may lead to the observed association between cataract surgery and AMD- rather than a cause/effect relationship between the surgery and AMD- example of confounding
strengths and weaknesses population based studies2
Strengths and WeaknessesPopulation Based Studies

Weaknesses:

  • CONFOUNDING
    • Cataracts that have not been removed may obscure features of AMD leading to the observation of lower prevalence of early or late AMD among eyes remaining phakic
    • AMD manifestations may have preceded cataract surgery rather than developed after cataract surgery among the eyes with prevalent AMD at the baseline exam (cross sectional data maybe affected by discovery bias)
    • Cataract surgery may have been done to attain a better view of the retina to facilitate diagnosis and treatment of advanced AMD in suspect cases
amd progression after cataract surgery clinical studies
AMD Progression after Cataract Surgery- Clinical Studies
  • Data from small case series has been inconsistent:
    • Pollack 1996: Increased risk among 47 patients with bilateral symmetric non-neovascular AMD s/p unilateral cataract surgery.
      • At 1 yr: 19% surgery eyes vs 4% phakic eyes had CNV; RR = 4.4
      • Small “N” and non-random assignment to surgery
    • Ambrecht 2000: No increased risk among 90 AMD eyes followed 3-5 mo post-op
      • No CNV developed
why is amd initially recognized shortly after cataract surgery in clinical practice
Why is AMD “initially” recognized shortly after cataract surgery in clinical practice?
  • Cataract surgery truly increases risk of AMD progression
  • Alternate possibilities:

a. Advanced AMD or moderate non-neovascular AMD may be present pre-op but clinician failed to detect its presence thru lenticular opacity

Vision change that contributed to recommendation for cataract surgery may have been due to progression of AMD rather than cataract

b. Associations may be observed by chance alone from time to time

amd progression after cataract surgery wilmer clinical series arch ophthalmol 2009 127 11 1412 1419
AMD Progression after Cataract SurgeryWilmer Clinical SeriesArch Ophthalmol, 2009;127(11):1412-1419

Colors/FA 1 wk pre + post-op, 3 and 12 mos post -op

BUT

only 3 of 65 eyes did so after week 1:

4.6% (95% CI 1.0%, 12.9%)

____________________________________________

9 of 71 non-neovascular AMD eyes developed CNV by 1 yr = 12.7% (95% CI 6.0%, 22.7)

2 of 61 eyes developed GA by 1 yr:

3.3% (95% CI 0.4−11.4%) BUT

there were no confirmed cases that developed after

1 week post-op

amd progression after cataract surgery wilmer clinical series
AMD Progression after Cataract SurgeryWilmer Clinical Series

Colors/FA 1 wk pre + post-op,3 and 12 mos post -op

Conclusion

Several cases of presumed progression may

have been present prior to cataract surgery

Low incidence rate of CNV or GA developing

between 1 wk and 1 yr after cataract surgery

does not support theory that surgery

accelerates AMD progression

case control study baatz 2008
Case-Control Study: Baatz 2008
  • Retrospective review of 1152 non-neovascular AMD eyes followed for 1 yr post cataract surgery vs 334 similar phakic eyes
  • CNV developed in 2.4% surgery vs 1.7% no surgery (OR = 1.3; 95% CI 0.5-3.2)
  • 4/28 surgery eyes with CNV discovered within 12 days of surgery; maybe overestimate of rate post-op

Assume OR of 1.3 is real—a calculated “number needed

to harm” analysis yields 146 cataract surgeries in eyes

with early AMD yields 1 additional person developing

CNV within 1 year because of the surgery.

australisn cataract srugery and age related macular degeneration study csamd
Australisn Cataract Srugery and Age-Related Macular Degeneration Study (CSAMD)
  • NO increased risk, over 3 yrs, of incident:
    • Late AMD
    • Early AMD
    • Soft/reticular drusen
  • 60% increased detection of RPE changes in operated eye within paired eye comparisons
slide17

AMD and Cataract in AREDS

Progression to Advanced AMD

  • Yearly Fundus Photographs
  • Photocoagulation for AMD
  • AREDS Definition of AMD Event

Cataract Surgery

  • Assessed Every Six Months

Mean Follow-up 9 years

Median age 67 at enrollment

slide18

AMD/Cataract: Analysis Methods

Three Different Analysis Approaches:

  • Cox Proportional Hazards Regression
  • -Time Dependent Covariates
  • (age, cat sg, AMD)
  • Matched Pair Analysis: Cases (Cataract
  • surgery) and Matched Controls (no sg)
  • Logistic Regression

Looking for Consistency of Findings

slide19

Analysis Methods

Eligible: all study eyes that were phakic at baseline (about 8050!)

Outcome: CNV or Central GA (~750)

Covariates:

  • Age at Baseline
  • Smoking Status
  • Gender
  • Race
  • AREDS Treatment (Active vs. Placebo)
  • AMD Severity on 9-Point Scale
slide20

Participant Characteristics

All Category

2, 3 & 4 Participants

N (people) 4577

Mean Age*68 yrs

Mean Follow-up8.8 yrs

% Female 59%

~1700 cataract Surgeries Performed

* At enrollment

slide21

Participant Characteristics

All Category

2, 3 & 4 Participants

N (people) 4577

Mean Age*68 yrs

Mean Follow-up8.8 yrs

% Female 59%

~1700 cataract Surgeries Performed

* At enrollment

cataract surgery and advanced amd cox proportional hazard model
Cataract Surgery and Advanced AMD: Cox Proportional Hazard Model*

Hazard

Ratio 95% CI

CNV

Central GA

Any GA

* Right eyes

cataract surgery and advanced amd logistic regression devt 5 yr
Cataract Surgery and Advanced AMD: Logistic Regression (devt 5/yr)*

Hazard

Ratio 95% CI

CNV

Central GA

Any GA

slide25

Analysis Methods

  • Cox Proportional Hazards Regression:
    • NO increased risk
  • Time Dependent Covariates
  • Cases (Cataract surgery) and Matched Controls
  • (no surgery):
    • ??Small increased risk of CNV
  • Logistic Regression:
    • NO increased risk

Three Different Analysis Approaches:

Consistent pattern of Harm is NOT SEEN for CNV or GA =

No clinically important increase in risk

summary amd and cataract literature
Summary: AMD and Cataract Literature
  • Eyes with varying levels of AMD can have vision and quality of life improvements with cataract surgery.
  • There is no clear evidence that AMD eyes are at clinically important greater risk of progression to advanced AMD following cataract surgery.
  • All individuals with AMD should be counseled as to the natural course of their disease and given reassurance that no great risk of disease acceleration has been identified with cataract surgery.
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