Prediction of Monocular Defocus Curves in Pseudophakia with Different Pupil Sizes

Background

With the widespread adoption of cataract surgery and lens replacement surgery, the optical performance of intraocular lenses (IOLs) has become increasingly critical in determining patients’ postoperative visual quality. Predicting clinical visual performance (such as visual acuity and defocus range) is an emerging area of interest in ophthalmology, particularly when discussing IOLs with different designs where their optical performance can vary with pupil size. However, existing prediction models often assume a fixed pupil size, overlooking this crucial variable’s impact in practical clinical applications.

In recent years, standardized procedures such as ANSI Z80.35-2018 and ISO 11979-7:2024 have introduced monocular defocus curves to more accurately classify IOLs (e.g., IOLs with extended depth of focus, or EDOF IOLs). While these standards recommend considering the influence of pupil size, methodologies to evaluate how changes in pupil size affect defocus curves are still underdeveloped. Existing research shortcomings are particularly evident in optical bench studies, which often use only a single pupil size (e.g., 3 mm or 4.5 mm), failing to align with the real-world variation in clinical data across different patient populations.

Addressing this knowledge gap, Antonio J. del Águila-Carrasco and his team sought to explore how to predict postoperative defocus curves under different pupil sizes based on optical bench measurements. This represents the first systematic study to predict monocular defocus curves across varying pupil sizes and compare them to clinical data.

Article Overview

The article, titled “Prediction of Monocular Defocus Curves in Pseudophakia with Different Pupil Sizes,” was authored by Antonio J. del Águila-Carrasco, Aixa Alarcon, Henk Weeber, and others. The authors are primarily affiliated with Johnson & Johnson Medtech’s divisions in the Netherlands and the United States, indicating substantial support from a major medical technology company. It was published in the February 1, 2025 issue of Biomedical Optics Express (Volume 16, Issue 2), a leading optics journal published by the Optica Publishing Group.

Research Process

Study Design and Procedure Overview

The research consisted of several critical phases, focusing on the comparison between optical bench experiments and clinical trial data:

1. Classification of IOLs and Experimental Subjects
   Six types of IOLs (all manufactured by Johnson & Johnson Vision) were included in the study. Three IOLs (ZCB00, ZXR00, ZLB00) were used to match optical bench data with clinical trial data, while the other three (ICB00, ZEN00V, ZFR00V) were utilized for defocus predictions based on the fitting equations derived in the study.

2. Optical Bench Measurements
   Using an average corneal eye (ACE) model that simulates the human cornea’s spherical and chromatic aberrations, the study analyzed how defocus metrics—Modulation Transfer Function Area (MTFA) and *Weighted Optical Transfer Function (WOTF)*—varied across a defocus range of -3.0 D to 0.5 D and pupil sizes of 2 mm, 3 mm, and 4.5 mm, in lenses with 20 D refractive power.

3. Clinical Data Collection
   Clinical data were collected from five studies sponsored by Johnson & Johnson Vision, evaluating postoperative monocular high-contrast visual acuity 3 to 6 months after surgery using the ETDRS eye chart. Patients were grouped into small pupil (≤3 mm), medium pupil (>3 mm but mm), and large pupil (≥4 mm) categories to assess real-world clinical visual performance.

4. Data Fitting and Analysis
   A power function curve-fitting method was employed for data analysis. MATLAB’s Curve Fitting Toolbox was used to calculate fitting parameters for each pupil size and optical metric. The Root Mean Square Error (RMSE) and coefficient of determination (R²) were used to assess the difference between simulated and clinical visual acuity. Bland-Altman plots were generated for further validation.

Study Subjects and Sample Size

The study included six IOL models evaluated on the optical bench and 69-206 patients categorized by pupil size. Due to the relatively small number of patients in the small-pupil group, analysis for this subgroup was somewhat limited.

Data Analysis and Algorithm Application

To achieve accurate predictions, the study utilized the following methods and metrics: - Power Function Model: Simulated visual acuity (VA) = a × (metric^b) + c, where a, b, and c are fitting parameters. - Relationship between Weighted Optical Transfer Function and Defocus Curve: This provided a more comprehensive frequency response, significantly improving the predictive model.

Key Findings

1. Optical Bench Experimental Results
   Both MTFA and WOTF successfully characterized the optical performance of IOLs across different pupil sizes and defocus ranges. R² values between optical bench measurements and clinical data consistently exceeded 0.85.

2. Data Fitting and Prediction Accuracy

   • MTFA Results: For medium and large pupils, the R² values between clinical and simulated visual acuity were close to 1, with RMSE ranging from 0.034 to 0.071. Accuracy was slightly lower for the small pupil group.
     
   • WOTF Results: WOTF showed higher accuracy for small pupils but was slightly outperformed by MTFA for large pupils.
     
   • Both metrics displayed high consistency in Bland-Altman plots, with 95% limits of agreement ranging between -0.1 and 0.1 logMAR, particularly for patients with pupil sizes above 3 mm.

3. Challenges with Small Pupil Group
   The small sample size in the small-pupil group limited prediction accuracy, reflected in slightly higher RMSE and less consistent Bland-Altman results compared to medium and large pupil groups.

4. Comparison of Monofocal and Multifocal IOL Performance
   Simulations for monofocal IOLs generally achieved higher accuracy compared to presbyopia-correcting (PC) multifocal IOLs. The differences may stem from the unique optical technologies (e.g., refractive or diffractive optics) employed in PC IOLs.

Conclusions and Significance

The study concludes that combining MTFA and WOTF metrics with variable pupil sizes in optical bench testing offers an effective method to predict postoperative defocus curves. This method enhances the ability to evaluate preclinical performance and provides theoretical guidance for selecting IOLs tailored to patients’ needs during surgery.

The research highlights the correlation between optical bench metrics and clinical outcomes under various pupil conditions, emphasizing the methodological significance of “pupil stratification” for preoperative predictions of patient-specific visual performance. This innovative approach offers a better differentiation of monofocal and multifocal IOLs’ strengths and could even inform mixed-implantation strategies (mix-and-match).

Research Highlights

• Innovative Pupil Stratification Analysis: First to incorporate the influence of pupil size into defocus curve prediction models.
  
• High-Correlation Metric Selection: Achieved improved correlation between optical bench data and clinical outcomes using MTFA and WOTF.
  
• Algorithm Applicability: The power function fitting and aggregated analysis provide potential value for designing future predictive algorithms.

Outlook and Improvements

The article suggests that future research should focus more on patients with smaller pupil diameters and further explore the feasibility of combining monocular defocus curves into binocular defocus models for IOL implantation strategies. Moreover, studying whether physical effects such as the Stiles-Crawford effect significantly influence different IOL designs could also be a promising direction.

Through this study, the authors propose a systematic framework for preclinical optical evaluation of IOLs, promoting a practical standardized tool to improve postoperative visual quality for cataract surgery patients.