Table 1.

Summary of HOAs and its association with dry eyes

Reference/study	Country	Study design	Groups and sample size	HOA measuring device	Level of evidence	Parameters for efficacy	Main result	Associations and remarks
Corneal higher-order aberrations (HOAs) in eyes with chronic ocular graft-versus-host disease Shimizu et al. 2020 [14]	Japan	Retrospective comparison study	30 eyes from 15 chronic ocular graft-versus-host disease (GVHD) cases and 30 eyes from 15 non-GVHD cases	Measured using anterior segment optical coherence tomography (AS-OCT)—OCT device	Level 3	Corneal HOAs, spherical aberrations (SA), and coma aberrations Correlation of corneal HOAs and visual acuity Correlation of International Chronic Ocular (ICO) severity score and visual acuity Correlation of corneal HOAs and ICO severity scores	The total and anterior HOAs at both 4- and 6-mm diameters in patients with GVHD were significantly higher than non-GVHD and healthy controls Total and anterior SA at both 4- and 6-mm diameters were significantly lower in patients with GVHD compared to control Total and anterior coma aberrations at 4-mm diameters were significantly higher in patients with GVHD vs without GVHD. Total coma aberrations at 6-mm was significantly higher in GVHD vs control Corneal HOAs were significantly higher in patients with GVHD compared to those without GVHD There was a statistically significant positive correlation between HOAs and visual acuity in all HOAs (total, anterior, and posterior) at 4 mm and 6 mm There was a statistically significant positive correlation between ICO severity score and visual acuity There was a statistically significant positive correlation between HOAs and ICO severity scores for all HOAs (total, anterior, and posterior) at 4 mm and 6 mm	There was no significant difference in posterior HOAs between groups There was no significant difference in SA between patients with GVHD and patients without GVHD. There was also no significant difference in posterior SA The correlation between posterior HOAs and ICO severity was significant but not as strong as total or anterior correlations
Wavefront analysis of higher order aberrations in dry eye patients Montes-Mico et al. 2004 [4]	Spain	Prospective comparison study	20 patients with dry eyes and 20 patients with normal eyes	Measured using a Zywave aberrometer (Bausch & Lomb, Irvine, CA) which is based on the Hartmann–Shack aberrometer—ray tracing device	Level 2	HOAs Hartmann–Shack and color-coded maps of total wavefront aberrations	HOAs in the patients with dry eye were significantly higher than in normal eyes for 4- and 6-mm diameter. Coma, spherical, and total aberrations for both 4- and 6-mm diameters were significantly greater in patients with dry eye compared to normal eyes In a 6-mm pupil for a normal and dry eye, quantitative analysis of the Hartmann–Shack image indicates a significant change in wavefront pattern in the dry eye compared to the normal eye	HOAs in general were found to be higher in patients with dry eye compared to normal eyes Statistical and quantitative analysis of the Hartmann–Shack image was not shown
Serial measurements of higher-order aberrations after blinking in patients with dry eye Koh et al. 2008 [15]	Japan	Prospective comparison study	20 patients with dry eyes Group A: 7 patients with superficial punctate keratopathy (SPK) in the central cornea Group B: 13 patients with SPK over the pupil and inferior paracentral cornea	Measured using the Hartmann–Shack wavefront aberrometer (Topcon Corp., Tokyo, Japan)—ray tracing	Level 2	Total HOAs, fluctuation index (FI), stability index (SI), coma, and spherical aberrations Serial changes in HOAs	Total HOAs, coma, and spherical aberrations were significantly higher in group B compared to group A In a 6-mm pupil for a normal and dry eye, quantitative analysis of the Hartmann–Shack image indicates a significant change in wavefront pattern in the dry eye compared to the normal eye In group A, total HOAs remained constant at each blink over 9 measurements taken over 10 s. In spherical aberrations, the aberrations were significantly higher at 7 and 9 s compared to at 2 s In group B, total HOAs remained relatively stable. For spherical aberrations, it was significantly higher at 9 s compared to at 2 and 4 s	There was no significant difference in FI and SI between groups There were no significant differences in coma aberrations in both groups over the 10 s
Higher order aberrations of the corneal surface after laser subepithelial keratomileusis Jung et al. 2014 [16]	South Korea	Prospective comparison study	16 patients with dry eyes and 15 patients with non-dry eyes that all underwent laser subepithelial keratomileusis (LASEK)	Measured using the Pentacam (Oculus; Optikgerate GmbH, Wetzlar, Germany)—OCT device	Level 2	Baseline characteristics Wavefront HOAs after blinking Correlation between HOAs and eye parameters	At baseline the dry eye group had significantly lower tear breakup time (TBUT), Schirmer test, and tear clearance rate (TCR) compared to the non-dry eye group. Ocular surface staining and ocular surface disease index (OSDI) scores were significantly higher in the dry eye group compared to non-dry eye group Ten seconds after blinking, there was a significant decrease in total HOAs RMS, coma, and trefoil aberrations in the non-dry eye group compared to the dry eye group Total HOA root mean square (RMS), coma, and trefoil aberrations were significantly higher 10 s after blinking compared to immediately after in the dry eye group only There was a significant negative correlation with total HOA RMS, coma, and trefoil aberrations with TBUT. There was a significant positive correlation with total HOA RMS, coma, and trefoil aberrations with OSDI	There was no significant difference in spherical aberrations between both groups. There was also no significant difference immediately after blinking for total HOA RMS, coma, trefoil, and spherical aberrations between both groups Lower TBUT scores were correlated with higher HOA RMS, coma, and trefoil aberrations. Higher OSDI scores were correlated with higher HOA, coma, and trefoil aberrations
Dynamic wavefront aberrations and visual acuity in normal and dry eyes Wang et al. 2009 [17]	China	Prospective comparison study	30 dry eyes and 27 normal controls	Measured using a WASCA system (Model 1369–202, Carl Zeiss Meditec, Germany)—ray tracing device	Level 2	Changes in wavefront aberrations Changes in visual acuity Mean instability of tRMS and hoRMS of wavefront aberrations	In general, wavefront aberrations changed and were more dynamic in patients with dry eye than normal eye patients Visual acuity changes were much more volatile patient to patient but changes in visual acuity on a logMAR scale had smaller amplitude changes in normal eyes The mean instability of tRMS and hoRMS in patients with dry eye was significantly greater than in the normal group The mean instability of visual acuity was also found to be higher in the dry eye group compared to the normal group	The changes in right and left eye differed in patients with dry eye. The RMS value tended to increase during periods of open eyes and returned to minimum after a blink. In the left eye, decreased about 4–5 s before returning to minimum after a blink There was no significant difference in post-LASIK eyes
Effect of tear film break-up on higher order aberrations of the anterior cornea in normal, dry, and post-LASIK eyes Lin et al. 2005 [18]	Taiwan	Prospective comparison study	40 post-LASIK eyes, 40 dry eyes, and 40 normal eyes	Measured using videokeratography—OCT device	Level 2	TBUT Corneal Topographies HOAs	TBUT was significantly less for dry eyes compared to post-LASIK and normal eyes Patients with normal and dry eyes showed a significant pattern of increased aberrations from post-blink through BUT There was a significant decrease in coma, trefoil, 3rd to 6th order aberrations after saline addition in both patients with normal and dry eyes	There was no significant difference in post-LASIK eyes
Tear film aberration dynamics and vision-related quality of life in patients with dry eye disease Denoyer et al. 2012 [19]	France	Prospective comparison study	40 patients with Sjögren syndrome/dry eyes and 40 patients with normal eyes	Measured using the KR-1 aberrometer (Topcon, Clichy, France)—dual OCT and ray tracing	Level 2	Baseline characteristics Aberration dynamics by group Area under the curve of modulation transfer function (aucMTF) Correlations	OSDI was significantly higher in dry eye vs normal eyes. TBUT and Schirmer test values were significantly lower in dry eye vs normal eyes There was a significant increase in total HOAs, coma, and trefoil aberrations in dry eyes compared to control eyes AucMTF was significantly decreased in patients with dry eye from 7 to 10 s after blinking compared to normal control A significant and negative correlation between TBUT and HOA progression index was found A significant and positive correlation between OSDI scores and HOA progression index was found
The impact of dysfunctional tear films and optical aberrations on chronic migraine Shetty et al. 2017 [20]	India	Prospective comparison study	30 patients with migraines and 30 control patients	Measured using the Optical Path Difference (OPDIII, Nidek, Japan)—dual OCT and ray tracing	Level 2	Baseline characteristics	Total aberrations, HOAs, coma, spherical, and objective scatter index (OSI) were significantly higher in the control group compared to the migraine group Lipiview interferometric coloric units (ICU) were significantly lower in the control group compared to the migraine group	There was no significant difference in trefoil aberrations and TBUT between the groups
Corneal fluorescein staining correlates with visual function in dry eye patients Kaido et al. 2011 [7]	Japan	Prospective comparison study	10 patients with Sjögren’s and SPK, 12 patients with Sjögren’s but no SPK, 10 control patients	Measured using the Hartmann–Shack wavefront aberrometer (Topcon Corp., Tokyo, Japan)—ray tracing device	Level 2	Tear function and vital staining scores Visual acuity parameters Ocular HOA parameters Serial changes in HOAs Correlation between visual acuity and HOAs	Schirmer value, fluorescein score, rose bengal score, and BUT were significantly different in the SPK+ group compared to control. Only Schirmer value was significantly lower in the SPK− group compared to control Visual maintenance ratio (VMR) was significantly lower in the SPK+ group compared to both SPK− and control groups. Variation of visual acuity was significantly higher in SPK+ group compared to both SPK− and control groups There was also a significant negative correlation between VMR and severity of epithelial damage. There was a significant positive correlation between variation of visual acuity and severity of epithelial damage Coma and total HOAs were significantly higher in the SPK+ group compared to the SPK− and control groups There was no significant change over the 10 s in coma, spherical, and total HOAs There were significant negative correlations between VMR and coma and total HOA	No statistical analysis between the SPK+ and SPK− groups were assessed There was no significant difference in spherical, FI, and SI between all groups The SPK+ was the only group with fluctuation during the measurement period but this was not significant
The impact of dry eye disease on visual performance while driving Deschamps et al. 2013 [21]	France	Prospective comparison study	20 patients with dry eyes and 20 patients with normal eyes	Measured using the dynamic aberrometer KR-1 (Topcon, Clichy, France)—dual OCT and ray tracing	Level 2	Driving test scores	The percentage of targets missed and average response time were significantly higher in patients with dry eye compared to control The progression index of total HOAs and trefoil aberrations were significantly higher in patients with dry eye compared to control There was a significantly positive correlation between response time and the progression index for HOAs as well as between response time and OSDI “symptom” subscale
Paradoxical increase of visual impairment with punctal occlusion in a patient with mild dry eye Koh et al. 2006 [22]	Japan	Case report	Patient with dry eye	Measured using the Hartmann–Shack wavefront aberrometer (Topcon Corp., Tokyo, Japan)—ray tracing device	Level 3	HOAs	There was an increase in HOAs post-blink after punctal plug placement	The change in HOAs corresponded to coma aberrations but not spherical aberrations
Effects of suppression of blinking on quality of vision in borderline cases of evaporative dry eye Koh et al. 2008 [23]	Japan	Case report	10 patients with short TBUT Normal stable group: stable pattern and small fluctuation pattern from normal eyes Normal-sawtooth group: sawtooth pattern of normal eyes Short TBUT group	Measured using the Hartmann–Shack wavefront aberrometer (Topcon Corp., Tokyo, Japan)—ray tracing device	Level 3	Serial changes in HOAs Total HOAs, FI, and SI	Total HOAs and coma aberrations were significantly higher from 5 to 9 s after a blink compared to those immediately after a blink Spherical aberrations were significantly higher from 6 to 9 s after a blink compared to immediately after The FI and SI in the short TBUT group were significantly higher than those in the normal-stable group	There was no significant difference in FI and SI between the short TBUT group and the normal-sawtooth group