Association of cataract history with dry eye disease signs and symptom

Introduction

Affecting 5–50% of the global population, dry eye disease (DED) is a multifactorial ocular surface disease characterized by the loss of tear film and accompanied by visual disturbances and discomfort.¹ The incidence of DED is known to increase with age: a recent meta-analysis estimated an incidence of 3.5% in the US population of 18 years and older compared with 7.8% in the US population of 68 years and older.² Similarly, cataracts are often considered a disease of aging: the prevalence of cataracts in the global population has been estimated to range from 3% in the 20–39-year-old population to over 50% in the over-60-year-old population.³ Despite the high prevalence of both DED and cataracts in the older population, there is limited knowledge on how cataracts and cataract surgery may affect the severity of DED signs and symptoms.

Cataract surgery may potentially affect DED through multiple mechanisms, including surgical trauma to the ocular surface, disruption of corneal innervation, and inflammatory responses that can alter tear film stability and composition.^4,5 Patients with pre-existing DED often express concerns about potential worsening of their symptoms following cataract surgery, making evidence-based counseling crucial for informed decision-making.⁶

While some reports suggest increased DED incidence following cataract surgery,^5,7 no studies have investigated how cataract surgery can exacerbate DED severity in patients with pre-existing DED. This study aims to provide a comprehensive assessment for the associations of cataracts and cataract history with severity of DED signs and symptoms through a secondary analysis of rich data from the Dry Eye Assessment and Management (DREAM) study.^8,9

Materials and Methods

DREAM Study

The DREAM study was a multicenter randomized placebo-controlled trial assessing the efficacy of omega-3 supplementation for the treatment of DED (NCT02128763). The details of the DREAM study design and its primary results have previously been reported.^8,9 The DREAM study was approved by the Institutional Review Board at each participating site, including approval from the University of Pennsylvania Institutional Review Board. The study followed the tenets of the Declaration of Helsinki, and informed consent was obtained from all participants. Only major features of DREAM study relevant to the study are described below.

Participant Selection

Individuals ≥18 years old with moderate-to-severe symptomatic DED, defined by having an Ocular Surface Disease Index (OSDI) of 25–80, were eligible for enrollment for the DREAM study. To enroll in the study, participants must have had symptoms of DED for at least 6 months prior to the initial screening visit and have used or had the desire to use artificial tears at least twice a day for the past two weeks before the initial screening visit. Participants also had to satisfy at least 2 of the following 4 criteria for dry eye signs in the same eye at two consecutive visits (screening and baseline visits within 2 weeks apart): 1) corneal fluorescein staining ≥4 (out of a possible 15 per eye); 2) conjunctival staining present ≥1 (out of a possible score of 6 per eye); 3) tear film break-up time (TBUT) ≤7 seconds; 4) Schirmer’s test ≥1 to ≤7 mm/5 minutes. Importantly, a recent history of ocular surgery, including laser-assisted in situ keratomileusis and cataract surgery within 6 months of the screening visit were ineligible for the study. The full comprehensive inclusion and exclusion criteria can be found in the DREAM Study protocol.⁹

Study Measures

Following the screening visit, relevant medical history and participant characteristics were collected at the baseline visit. Medical history included self-reported history of smoking, rosacea, Sjögren’s syndrome, peripheral vascular disease, thyroid dysfunction, hypertension, rheumatoid arthritis, irritable bowel, osteoarthritis, hypercholesterolemia, and depression. Other components of physical and mental health, including depression were assessed. Lastly, the use of ongoing treatments for dry eye disease, including, but not limited to artificial tears, cyclosporine drops, warm lid soaks, punctal plugs, and steroid eye drops, were recorded. Participants self-reported either no history of cataracts, ongoing cataracts (clinically diagnosed cataracts without surgical intervention), or the presence of a pseudophakic or aphakic eye (representing a history of cataract surgery >6 months prior to enrollment).

Outcome measures of dry eye symptoms and signs were assessed at baseline, 6 months, and 12 months. Dry eye symptoms were measured using the OSDI score and the Brief Ocular Discomfort Inventory (BODI) score. The OSDI score ranged from 0–100, with a score of 0 indicating the lack of any ocular symptoms and 100 indicating the most severe symptoms of dry eye.¹⁰ The BODI score uses a similar rating system, with a rating scale of 0–100; it is often used as an alternative measure to OSDI for scoring dry eye symptoms, especially for patients with severe DED.¹¹ Dry eye signs in each eye were evaluated using 6 different dry eye sign measures including: TBUT, Schirmer’s test, corneal staining score, conjunctival staining score, meibomian gland dysfunction, and tear osmolarity. TBUT was measured as the time it took for a break to appear in the tear film following a blink. Schirmer’s test involved using paper strips placed in the lower eyelid to measure the distance of wetting on the paper in 5 minutes. Corneal staining was performed using fluorescein staining, and the staining score was determined using the National Eye Institute grading scale, grading each of 5 cornea sections with a score of 0–3 and combining the score for a maximum of 15 points.¹² Similarly, conjunctival staining score was evaluated on a scale of 0–3 in both the temporal and nasal sections of the conjunctiva with a maximum total score of 6 points. MGD was assessed using a TearScience Meibomian Gland Evaluator™ on silt-lamp examination, which evaluated the consistency of secretions and plugging on a 0–3 scale with a maximum total score of 6 points. Tear osmolarity was evaluated using a TearLab™ Osmolarity System (San Diego, CA), which measured the osmolarity level of the tear film from a range of 275 to 400 mOsm/L. Higher scores indicate more severe DED signs for corneal staining, conjunctival staining, MGD, and tear osmolarity, whereas lower scores indicate more severe DED signs for TBUT and Schirmer’s test. A composite severity score of DED signs from 0–1 was generated with the aforementioned measures by using a modified method from previous studies.^13–15

Statistical Analysis

We evaluated associations between cataract history at baseline and DED symptoms and signs by grouping participants into three groups: 1) no history of cataracts; 2) ongoing cataracts; and 3) previous history of cataract surgery. We compared the DED signs and symptoms among these three cataract history groups using univariate and multivariate regression analyses. Multivariate analyses were adjusted for factors previously found to be associated with DED severity in the DREAM study, including age, gender, race, ethnicity, smoking status, Sjögren’s syndrome, facial rosacea, rheumatoid arthritis, peripheral artery disease, and depression (defined by a mental health component scale ≤42).^16–20 These comparisons were based on combined data from baseline, 6 and 12 months, with correlation from repeated measures and inter-eye correlation (for comparison of signs) accounted for by using generalized estimating equations. Since the DREAM study did not find a significant treatment effect from ω-3 supplementation on DED symptoms and signs, these analyses were conducted on the two original study groups combined (ω-3 supplementation and placebo).⁸ Missing data were handled using available case analysis, with participants included if they had data for the specific outcome being analyzed.

All statistical analyses were performed using SAS version 9.4 (SAS Institute, Cary, NC). Two-sided P<0.05 was considered statistically significant without adjustment for multiple comparisons.

Results

Participant Characteristics and Medical History

Among the 535 participants (1070 eyes) enrolled in the DREAM study, 646 eyes (60%) had no history of cataracts, 244 eyes (23%) had ongoing cataracts, and 180 eyes (17%) had a history of cataract surgery >6 months prior (ie, pseudophakic/aphakic). Following the baseline evaluation, 479 participants (89.5%) completed the 6-month follow-up evaluation, and 486 (90.8%) participants completed the 12-month follow-up evaluation.

A comprehensive comparison of the baseline participant characteristics among the three cataract history groups can be found in Table 1. The three groups were similar in gender (P = 0.07). However, participants with a history of cataract surgery were significantly older (P < 0.0001), less likely to identify as Hispanic or Latino (P < 0.0001), less likely to have never smoked (P = 0.03), and more likely to have ongoing hypertension (P < 0.0001), osteoarthritis (P < 0.0001) and hypercholesterolemia (P < 0.0001) than participants with ongoing cataracts or no history of cataracts. A significantly higher percentage of participants with a history of cataract surgery and with ongoing cataracts self-identified their race as white (P < 0.0001), have ongoing facial rosacea (P = 0.05), and have ongoing diabetes (P = 0.04) compared to participants with no history of cataracts. The prevalence of other notable comorbidities such as Sjögren’s syndrome, peripheral vascular disease, thyroid dysfunction, rheumatoid arthritis, irritable bowel syndrome, and depression were similar across the three groups (all P > 0.05).

At baseline, participants with a history of cataract surgery were more likely to use artificial tears or gels (93% vs 78% vs 76%, respectively; P = 0.001), lubricating ointment (22% vs 10% vs 10%, respectively; P = 0.03), and cyclosporine drops (31% vs 27% vs 14%, respectively; P<0.001) compared to participants with ongoing cataracts or no history of cataracts (Table 2). There was no significant difference in the use of other dry eye therapeutics among the three groups.

Table 2 Comparison of Treatments for Dry Eye Disease by Baseline Cataract Status

Cataract History and DED Signs and Symptoms

In the univariate analysis (Table 3), corneal staining scores were significantly worse in eyes with a history of cataract surgery compared to eyes with ongoing cataracts and eyes with no history of cataracts (mean ± SE: 4.1 ± 0.3 vs 3.6 ± 0.2 vs 3.1 ± 0.1 respectively; P=0.005). However, this difference became non-significant after adjusting by factors previously found to be associated with DED severity (adjusted mean ± SE: 3.6 ± 0.3 vs 3.3 ± 0.2 vs 3.4 ± 0.1 respectively; P = 0.72) (Table 4) and was not significant after being adjusted by age alone (adjusted mean ± SE: 3.6 ± 0.3 vs 3.4 ± 0.2 vs 3.4 ± 0.2, respectively; P = 0.70) (Supplementary Table 1). In univariate analysis, tear osmolarity was significantly worse in eyes with a history of cataract surgery than in eyes with ongoing cataracts and eyes with no history of cataracts (mean ± SE: 305.7 ± 1.4 vs 304.0 ± 1.1 vs 301.8 ± 0.7 respectively; P=0.03) but was not significant in multivariate analysis (adjusted mean ± SE: 304.7 ± 1.5 vs 303.6 ± 1.1 vs 302.5 ± 0.8, respectively; P = 0.42) (Table 4). MGD was not different among the three groups in univariate analysis (P=0.67), but in multivariate analysis (Table 4), the MGD score was significantly higher in eyes with no history of cataracts than in eyes with cataracts and eyes with a history of cataract surgery (adjusted mean ± SE: 3.1 ± 0.1 vs 2.7 ± 0.1 vs 2.6 ± 0.2, respectively; P = 0.02). There was no significant difference in TBUT, Schirmer’s test, conjunctival staining score, and composite dry eye severity (all P > 0.11) among the 3 groups in both univariable and multivariable analyses. Cataract history was not associated with any dry eye symptoms, assessed by OSDI (P=0.98), BODI (P = 0.18), and BODI pain scores (P = 0.46) (Table 3).

Table 3 Univariate Analysis for the Comparison of DED Symptoms and Signs at Baseline, 6 month, 12 month Combined by Baseline History of Cataract

Table 4 Multivariate Analysis for the Comparison of DED Symptoms and Signs at Baseline, 6 month, 12 month Combined by Baseline History of Cataract

Discussion

Our study evaluated associations between cataract history and DED severity among well-characterized participants with moderate-to-severe DED. While corneal staining and tear osmolarity were significantly worse in participants with a history of cataract surgery, these associations were not significant upon adjusting for age and other factors previously found to be associated with DED. Interestingly, our study found an atypical association between cataract history and MGD, where eyes with a history of cataract surgery tended to have less severe MGD than eyes with no history of cataracts.

Contrary to studies suggesting increased DED incidence after cataract surgery, our findings indicate that DED exacerbations are likely transient.^21,22 Our study found that a history of cataract surgery was not independently associated with worse DED signs and symptoms in participants with moderate-to-severe DED. The use of eye drops, particularly ones containing benzalkonium chloride preservatives, are commonly administered during the postoperative period following cataract surgery. Studies have shown that preservative eye drops can significantly increase DED signs compared to non-preservative eye drops in patients not previously affected by DED.^23,24 It is plausible that our patients may have experienced increased DED signs and symptoms immediately after cataract surgery due to a combination of the surgical trauma and usage of postoperative preservative eye drops, which were alleviated after the discontinuation of preservative eye drops in the following months, allowing for the recovery of the ocular surface.

Our findings suggest that exacerbations of DED signs and symptoms associated with cataract surgery are time-limited and reversible. Previous research indicates that corneal sensitivity and tear functions return to preoperative levels within 1–3 months post-surgery.^25,26 This theorized timeframe of recovery is consistent with other recent studies as well: a 2024 study of patients with mild-to-moderate DED found that after six months of cataract surgery, signs of dry eye significantly improved compared to signs of dry eye immediately post-surgery in both patients who used eye drops with or without preservatives postoperatively.²⁷ While this seems to suggest that the ocular surface of patients with DED will eventually recover from cataract surgery, it is important to note that it is yet to be elucidated whether these transient exacerbations of DED signs and symptoms post-surgery affect eyes with pre-existing DED for longer than healthy eyes. The presence of significantly worse corneal staining scores in participants with a history of cataract surgery that disappeared upon adjusting solely for age suggests that DED severity, if associated with cataract surgery, is more related to the age of the patient population than the surgery itself. The lack of significant difference in DED signs and symptoms in patients with ongoing cataracts and patients with no history of cataracts also suggests that the development of the cataract itself does not increase DED severity.

Interestingly, in our study, MGD was significantly less severe in participants with a history of cataract surgery than patients with no history of cataracts. This is counter to what the prevailing consensus is in the literature—studies in the literature suggest that there is an exacerbation of MGD, with lower meibum expressibility and lower meibum quality, in patients following cataract surgery.²⁸ One possible explanation of our findings is that in the months following cataract surgery, and before enrollment, participants with a history of cataract surgery had time for any damaged meibomian glands to heal. Past studies have shown that MGD aggravation due to cataract surgery normally resolves by 3 months post-surgery.²⁹ Some studies report that meibomian gland expressibility and meibum quality return as soon as 1 month post-operatively.³⁰ Additionally, in our study, participants with a history of cataract surgery were significantly more likely to use cyclosporine A eye drops as treatment for DED. Cyclosporine A is a calcineurin inhibitor known to suppress T-cell mediated immune responses, and these anti-inflammatory effects may alleviate MGD.³¹ For example, a randomized control trial of 33 patients with MGD found that patients who were randomized to topical cyclosporine A had significantly lower number of meibomian gland inclusions, improved tarsal telangiectasis, and improved lid margin vascularity—all indications of MGD severity—compared to the placebo group at 3 months.³² This seems to indicate that cyclosporine A not only treats the accompanying DED signs and symptoms but can also treat the underlying MGD as well. However, while the greater usage of cyclosporine A in participants with a history of cataract surgery can be a possible explanation of our finding, we cannot conclusively determine why participants with a history of cataract surgery had significantly better MGD compared to the other two groups. Future studies are needed to better understand the role cataract surgery plays in MGD in patients with DED.

There were some limitations to our study. First, cataract history was self-reported, which may introduce recall bias. Second, participants who enrolled in the DREAM study could not have undergone cataract surgery within 6 months of the initial baseline visit. Therefore, we could only evaluate the long-lasting association of cataract surgery with DED severity. The short-term effects of cataract surgery on DED severity could be investigated through a future study which includes patients with a recent history of cataract surgery (ie <6 months). Third, we did not collect data on specific surgical techniques or intraoperative medications that might influence DED outcomes. Fourth, the DREAM study only enrolled patients with moderate-to-severe DED; thus, we were unable to assess how cataract surgery is associated with DED severity in patients with mild DED. Fifth, we did not adjust for multiple comparisons across many dry eye outcome measures, which may increase the risk of Type I error. However, our primary analyses focused on clinically meaningful differences rather than statistical significance alone. Additionally, our study did not evaluate the molecular and cellular effects of cataract surgery on the tear film. Future studies that investigate how cataract surgery impacts the cornea on a cellular level in patients with DED would be helpful in our understanding of how cataract surgery impacts DED. A study of 48 eyes that underwent phacoemulsification found that while TBUT improved significantly and returned to pre-operative levels 1-month following the surgery, goblet cell density was significantly decreased at 1 day, 1 month, and 3 months post-surgery.³³ Thus, while the exacerbation of signs and symptoms of DED may be transiently induced in cataract surgery, the decrease in goblet cell density post-surgery could have a longer-lasting effect on the eyes of DED patients. Finally, in our study, participants with a history of cataract surgery were significantly more likely to use artificial tears, gels, cyclosporine drops, and lubricating ointment than participants without history of cataracts. These therapeutics are known to attenuate DED signs and symptoms (eg, artificial tears lower OSDI scores) and thus may have masked the effect of phacoemulsification on DED severity in our participants.^34–36 Moreover, past studies have shown that the usage of topical medications such as cyclosporine A or artificial tears has improved DED symptoms (as measured by OSDI) in patients post-phacoemulsification.³⁷ Future studies that evaluate the microscopic ocular surface changes in post-cataract surgery patients with DED can better evaluate the effect of cataract surgery on DED signs and symptoms without confounders (ie, therapeutics alleviating dry eye signs and symptoms).

Conclusions

In patients with moderate-to-severe DED, cataracts and a history of cataract surgery were not independently associated with more severe DED symptoms and signs. However, this study was limited to long-term effects because participants with recent cataract surgery (<6 months) were excluded. This lack of association suggests that increased DED severity following phacoemulsification is either related to patient age and/or are transient in DED patients. The use of anti-inflammatory eye drops may be able to mitigate MGD after cataract surgery in patients with moderate-to-severe DED. However, this merits further investigation. Additional studies are needed to better understand how cataract surgery affects DED severity and MGD in patients with DED.