ASCRS News: EyeWorld Journal Club
Fall 2024

by Ryan Wallace, MD,* Sanchay Gupta, MD, MBA,* Uma Balakrishnan, MD,* Cullen Eye Institute residents, Masih Ahmed, MD, Residency Program Director
*All authors contributed equally to this work.

Keratoconus can result in a highly aberrated optical system and degraded visual acuity.¹ Currently, available methods to decrease the amount of higher order aberrations (HOAs) and lower order aberrations (LOAs), such as rigid contact lenses, scleral contact lenses, and intracorneal ring segments, act at the corneal plane. However, another well-known approach to decreasing optical aberrations is the pinhole effect, and previous case studies have demonstrated improved visual acuity in eyes with irregular corneas with a small aperture piggyback IOL.^2,3 In this study, van den Berg et al. used Zernike analysis with different pupil sizes to model the effect of a 1.6 mm aperture on HOAs and predict visual acuity in patients with keratoconus. The authors also provided a case report of an individual with keratoconus who underwent cataract surgery with implantation of the Bausch + Lomb IC-8 Apthera small aperture IOL (1.36 mm) as proof-of-concept. A lens-based strategy to correct HOAs in patients with keratoconus would be beneficial for elderly patients with cataracts and those who are unable to easily use or tolerate contact lenses.

Methods

This study was a retrospective chart review of all patients with keratoconus seen at Storm Eye Institute, Medical University of South Carolina between July 2016 and October 2022. The IC-8 Apthera IOL received pre-market approval from the FDA on July 22, 2022 (CDRH, 2022).⁴

Patients with keratoconus were categorized based on their Amsler-Krumeich classification, which is determined by the amount of induced myopia and/or astigmatism, average keratometry values, and corneal pachymetry as measured with Scheimpflug tomography (Pentacam HR, Oculus). Eyes with nystagmus or confounding corneal pathology were excluded from the study. 

The Zernike analysis function on the Pentacam HR was used to calculate LOAs and HOAs up to the 6th order with a natural photopic pupil size and pupil aperture of 6, 4, and 2 mm. These data were extrapolated to estimate the amount of HOAs in each eye with a 1.6 mm aperture to model the effect of a pinhole lens. Dynamic sciascopy (OPD-Scan III, Nidek) was used to predict corrected distance visual acuity (CDVA). Pearson correlation between LOAs and HOAs with CDVA was performed with a 95% confidence interval.

In the single patient with keratoconus who underwent cataract surgery with IC-8 Apthera IOL implantation, the authors reported corneal and whole-eye HOAs with Scheimpflug tomography and ray tracing (iTrace, Tracey Technologies).

Results

This retrospective chart review included 56 keratoconus patients classified into mild (Amsler-Krumeich stage I), moderate (stage II), or severe disease (stages III and IV). There were no significant differences between age or gender across these 3 groups. As expected, when comparing to patients with mild disease, baseline Kmax values were higher in the moderate group and highest in the severe group.

Significant correlations were observed between CDVA and total HOAs, LOAs, spherical aberration, coma, and trefoil under natural photopic conditions. Data on HOAs obtained from 6, 4, and 2 mm apertures were used to extrapolate HOAs for the 1.6 mm effective aperture of the IC-8 Apthera lens at the corneal plane. After stratifying by disease severity, the authors found that at larger effective apertures, HOAs differed modestly between groups (severe eyes had higher HOAs compared to moderate eyes, which had higher HOAs compared to mild eyes). However, this relative difference between groups decreased with decreasing aperture size and appeared to nearly converge at the 1.6 mm aperture. The average theoretical root mean square (RMS) value for the extrapolated HOAs at 1.6 mm aperture size in the study was 0.12 μm. 

The authors described a case of a 66-year-old female who underwent cataract surgery and implantation of the IC-8 Apthera IOL. Preoperatively, the measured corneal RMS HOAs were 0.72 μm and, using the same methods as with the patients above, they estimated 0.05 μm with a 1.6-mm aperture at the corneal plane. They reported an improvement in UDVA from 20/150 to 20/30 and measured final total RMS HOAs of 0.039 μm.

Discussion

In their retrospective study of 56 eyes with keratoconus, van den Berg et al. conducted Zernike analysis to obtain the corneal aberrations of three different simulated pupil diameters. They discussed how although higher order aberrations are accountable for a significant portion of the poor vision in keratoconus, lower order aberrations play a substantial role as well.

The data show a significant positive correlation between HOA and logMAR visual acuity in keratoconus patients under natural pupil photopic conditions. More impressively, the results provided evidence that the extrapolated 1.6 mm pupil size reduces HOA in keratoconus patients to a level consistent with that of the normal population with a 4 mm pupil size. Even the most severe of keratoconus patients experience a decrease in HOA down to 0.20 μm at a 1.6 mm pupil. In their discussion, the authors further solidify their case by citing a study involving the small aperture piggyback IOL use and its impact on quality of vision.³

This study has multiple strengths, including sound methodology and being highly reproducible. The authors clearly provided the reasoning for the variables included, how they carried out their analysis, and the data that resulted. Their own discussion was well thought out, and the logical conclusions from the data were easy to follow.

The authors mentioned a caveat that reducing total RMS HOAs with a 1.6 mm aperture does not guarantee high contrast vision due to residual HOA over the entrance pupil. One must consider the area outside the annular mask of the IOL as a potential for further degradation. The outer diameter of the opaque annular mask is 3.23 mm. In conditions where a pupil is dilated beyond this, aberrant light may enter outside the filtered area and affect vision quality. 

A limitation of the study is that it is an extrapolation based only on retrospective data. Although their findings were consistent with previous literature and their single case of IOL implantation, making extrapolated data from retrospective sources can still lead to significant bias compared to prospective data. Nevertheless, their case report of the single patient lays the groundwork well for a prospective study involving the small aperture IOL in keratoconus patients. It is also important to note that the preoperative data in this patient showed the estimated corneal RMS HOA to be 0.05 μm. Postoperatively, total eye RMS HOA was evaluated, which was 0.039 μm. Total eye RMS HOA data takes internal HOA into account as opposed to just corneal HOA, but this does not seem to cause much deviance.

The exclusion criteria only included corneal pathology and nystagmus. There was no mention of posterior segment or other pathology (such as a cataract) that would also affect vision. Two patients with low HOAs appeared to have poor vision, and addressing the causes of their decreased vision might have been helpful. 

The authors also provided a discussion in response to concerns about the pinhole IOL. In response to the concern that a pinhole may decrease brightness sensitivity, the authors cited corneal inlay data regarding enhanced brightness perception in the eye with the pinhole inlay.⁵ The authors stated that the IOL has not been found to interfere with visualization of the retina. Anecdotal reports exist regarding the ability to conduct retinal surgery behind pinholes, and this is an area that will need to be further elucidated.⁶

Overall, this study is a valuable addition to the growing body of work supporting the application of the pinhole effect to improve visual outcomes in patients with keratoconus. The option for a lens-based reduction of optical aberrations in patients with keratoconus appears promising, particularly for those patients approaching the age for cataract extraction and others who may not be able to tolerate contact lenses. As this specific small aperture IOL was approved for use shortly before this study’s conclusion, we look forward to further real-world clinical data demonstrating the efficacy of this or other similar small aperture devices for patients with keratoconus. 

---

Prediction of the small aperture intraocular lens on visual acuity in patients with keratoconus

van den Berg RM, et al. J Cataract Refract Surg. 2024;50:930–935.

• Purpose: To investigate the impact of corneal higher order aberrations (HOAs) on predicted corrected distance visual acuity (CDVA) in patients with keratoconus at varying simulated pupil apertures.
• Setting: Ophthalmology Clinics, Medical University of South Carolina, USA.
• Design: Retrospective chart review study.
• Methods: 56 eyes with keratoconus were examined using Scheimpflug tomography during routine examinations prior to medical intervention. The severity of keratoconus was graded using the Amsler-Krumeich classification. Zernike analysis was used to obtain corneal aberrations using simulated pupil diameters of 6, 4, and 2 mm. These data were extrapolated to obtain the total RMS HOAs for a 1.6-mm simulated pupil to evaluate the potential effect of a small aperture intraocular lens. Correlation analysis was used to study the impact and relative contributions of HOAs on CDVA. Convolution of HOAs from OPD-Scan III (Nidek) provided a clinical method to predict CDVA with different simulated pupil sizes in corneas with irregular astigmatism.
• Results: There were statistically significant positive correlations between photopic CDVA and the magnitude of total and individual (coma, spherical aberration, and trefoil) HOAs in this cohort of keratoconus subjects. A keratoconus case with the small aperture IOL confirms the improvement in vision due to the pinhole effect.
• Conclusion: The small aperture IOL is expected to markedly reduce aberrations in keratoconus patients up to Amsler-Krumeich class 4 severity to levels consistent with the levels seen in healthy patients. Convolution of corneal HO aberrations with the ETDRS chart provides a useful simulation of the impact of pinhole optics in aberrated eyes.

---

References

1. Kosaki R, et al. Magnitude and orientation of Zernike terms in patients with keratoconus. Invest Ophthalmol Vis Sci. 2007;48:3062–3068.
2. Salmon TO, van de Pol C. Normal-eye Zernike coefficients and root-mean-square wavefront errors. J Cataract Refract Surg. 2006;32:2064–2074.
3. Trindade CC, et al. New pinhole sulcus implant for the correction of irregular corneal astigmatism. J Cataract Refract Surg. 2017;43:1297–1306.
4. Center for Devices and Radiological Health. July 22, 2022. Premarket approval letter for the IC-8^® Apthera^TM Intraocular Lens (IOL) – P210005. United States Food and Drug Administration. www.accessdata.fda.gov/cdrh_docs/pdf21/P210005A.pdf
5. Manzanera S, et al. Adaptation to brightness perception in patients implanted with a small aperture. Am J Ophthalmol. 2019;197:36–44.
6. Dick HB, Gerste RD. Future intraocular lens technologies. Ophthalmology. 2021;128:e206–e213. 

Contact 

Ahmed: Masih.Ahmed@bcm.edu