Longitudinal Study of Age-Related Cataract Using Dynamic Light Scattering. Loss of α-Crystallin Leads to Nuclear Cataract Development

Manuel B. Datiles, Rafat R. Ansari, Junko Yoshida, Holly Brown, Andrea I. Zambrano, Jing Tian, Susan Vitale, J. Samuel Zigler, Frederick L. Ferris, Sheila K West, Walter J. Stark

Research output: Contribution to journalArticle

Abstract

Purpose: To conduct a longitudinal study on age-related nuclear cataracts using dynamic light scattering (DLS) to determine if cataract progression is associated with loss of the unbound form of the lens molecular chaperone protein, α-crystallin. Design: Natural history and cohort study. Participants: Patients 30 years of age or older of either gender seeking treatment at the Wilmer Eye Institute Cornea-Cataract Department. Methods: All patients underwent a comprehensive dilated eye examination every 6 months, including slit-lamp grading of their lenses using the Age-Related Eye Disease Study (AREDS) clinical lens grading system and obtaining an estimate of unbound α-crystallin level in the nucleus, the α-crystallin index (ACI), using the National Aeronautics and Space Administration-National Eye Institute DLS device. We used a random effects statistical model to examine the relationship of lens opacity changes over time with ACI changes. Main Outcome Measures: α-Crystallin Index (ACI) and AREDS nuclear cataract grade. Results: Forty-five patients (66 eyes) 34 to 79 years of age with AREDS nuclear lens grades of 0 to 3.0 were followed up every 6 months for a mean of 19 months (range, 6-36 months). We found that lenses with the lowest baseline levels of ACI had the most rapid progression of cataracts, whereas lenses with higher ACI at baseline had no or slower cataract progression. Lenses that lost α-crystallin at the highest rates during the study also had faster progression of nuclear cataracts than lenses with a slower rate of ACI loss. Kaplan-Meier survival curves showed that lenses with the lowest initial ACI had the highest risk of undergoing cataract surgery. Conclusions: This longitudinal study corroborates our previous cross-sectional study finding that higher levels of unbound α-crystallin as assessed by ACI are associated with lower risk of cataract formation and that loss of ACI over time is associated with cataract formation and progression. This study suggested that assessment of ACI with the DLS device could be used as a surrogate for lens opacity risk in clinical studies, and for assessing nuclear cataract events in studies where cataract development may be a side effect of a drug or device.

Original languageEnglish (US)
JournalOphthalmology
DOIs
StateAccepted/In press - Jun 17 2015

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Crystallins
Cataract
Longitudinal Studies
Lenses
Eye Diseases
Equipment and Supplies
Dynamic Light Scattering
National Eye Institute (U.S.)
United States National Aeronautics and Space Administration
Molecular Chaperones
Kaplan-Meier Estimate
Statistical Models
Drug-Related Side Effects and Adverse Reactions
Natural History
Cornea
Cohort Studies

ASJC Scopus subject areas

  • Ophthalmology

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Longitudinal Study of Age-Related Cataract Using Dynamic Light Scattering. Loss of α-Crystallin Leads to Nuclear Cataract Development. / Datiles, Manuel B.; Ansari, Rafat R.; Yoshida, Junko; Brown, Holly; Zambrano, Andrea I.; Tian, Jing; Vitale, Susan; Zigler, J. Samuel; Ferris, Frederick L.; West, Sheila K; Stark, Walter J.

In: Ophthalmology, 17.06.2015.

Research output: Contribution to journalArticle

Datiles, Manuel B. ; Ansari, Rafat R. ; Yoshida, Junko ; Brown, Holly ; Zambrano, Andrea I. ; Tian, Jing ; Vitale, Susan ; Zigler, J. Samuel ; Ferris, Frederick L. ; West, Sheila K ; Stark, Walter J. / Longitudinal Study of Age-Related Cataract Using Dynamic Light Scattering. Loss of α-Crystallin Leads to Nuclear Cataract Development. In: Ophthalmology. 2015.
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abstract = "Purpose: To conduct a longitudinal study on age-related nuclear cataracts using dynamic light scattering (DLS) to determine if cataract progression is associated with loss of the unbound form of the lens molecular chaperone protein, α-crystallin. Design: Natural history and cohort study. Participants: Patients 30 years of age or older of either gender seeking treatment at the Wilmer Eye Institute Cornea-Cataract Department. Methods: All patients underwent a comprehensive dilated eye examination every 6 months, including slit-lamp grading of their lenses using the Age-Related Eye Disease Study (AREDS) clinical lens grading system and obtaining an estimate of unbound α-crystallin level in the nucleus, the α-crystallin index (ACI), using the National Aeronautics and Space Administration-National Eye Institute DLS device. We used a random effects statistical model to examine the relationship of lens opacity changes over time with ACI changes. Main Outcome Measures: α-Crystallin Index (ACI) and AREDS nuclear cataract grade. Results: Forty-five patients (66 eyes) 34 to 79 years of age with AREDS nuclear lens grades of 0 to 3.0 were followed up every 6 months for a mean of 19 months (range, 6-36 months). We found that lenses with the lowest baseline levels of ACI had the most rapid progression of cataracts, whereas lenses with higher ACI at baseline had no or slower cataract progression. Lenses that lost α-crystallin at the highest rates during the study also had faster progression of nuclear cataracts than lenses with a slower rate of ACI loss. Kaplan-Meier survival curves showed that lenses with the lowest initial ACI had the highest risk of undergoing cataract surgery. Conclusions: This longitudinal study corroborates our previous cross-sectional study finding that higher levels of unbound α-crystallin as assessed by ACI are associated with lower risk of cataract formation and that loss of ACI over time is associated with cataract formation and progression. This study suggested that assessment of ACI with the DLS device could be used as a surrogate for lens opacity risk in clinical studies, and for assessing nuclear cataract events in studies where cataract development may be a side effect of a drug or device.",
author = "Datiles, {Manuel B.} and Ansari, {Rafat R.} and Junko Yoshida and Holly Brown and Zambrano, {Andrea I.} and Jing Tian and Susan Vitale and Zigler, {J. Samuel} and Ferris, {Frederick L.} and West, {Sheila K} and Stark, {Walter J.}",
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AU - Datiles, Manuel B.

AU - Ansari, Rafat R.

AU - Yoshida, Junko

AU - Brown, Holly

AU - Zambrano, Andrea I.

AU - Tian, Jing

AU - Vitale, Susan

AU - Zigler, J. Samuel

AU - Ferris, Frederick L.

AU - West, Sheila K

AU - Stark, Walter J.

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N2 - Purpose: To conduct a longitudinal study on age-related nuclear cataracts using dynamic light scattering (DLS) to determine if cataract progression is associated with loss of the unbound form of the lens molecular chaperone protein, α-crystallin. Design: Natural history and cohort study. Participants: Patients 30 years of age or older of either gender seeking treatment at the Wilmer Eye Institute Cornea-Cataract Department. Methods: All patients underwent a comprehensive dilated eye examination every 6 months, including slit-lamp grading of their lenses using the Age-Related Eye Disease Study (AREDS) clinical lens grading system and obtaining an estimate of unbound α-crystallin level in the nucleus, the α-crystallin index (ACI), using the National Aeronautics and Space Administration-National Eye Institute DLS device. We used a random effects statistical model to examine the relationship of lens opacity changes over time with ACI changes. Main Outcome Measures: α-Crystallin Index (ACI) and AREDS nuclear cataract grade. Results: Forty-five patients (66 eyes) 34 to 79 years of age with AREDS nuclear lens grades of 0 to 3.0 were followed up every 6 months for a mean of 19 months (range, 6-36 months). We found that lenses with the lowest baseline levels of ACI had the most rapid progression of cataracts, whereas lenses with higher ACI at baseline had no or slower cataract progression. Lenses that lost α-crystallin at the highest rates during the study also had faster progression of nuclear cataracts than lenses with a slower rate of ACI loss. Kaplan-Meier survival curves showed that lenses with the lowest initial ACI had the highest risk of undergoing cataract surgery. Conclusions: This longitudinal study corroborates our previous cross-sectional study finding that higher levels of unbound α-crystallin as assessed by ACI are associated with lower risk of cataract formation and that loss of ACI over time is associated with cataract formation and progression. This study suggested that assessment of ACI with the DLS device could be used as a surrogate for lens opacity risk in clinical studies, and for assessing nuclear cataract events in studies where cataract development may be a side effect of a drug or device.

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