Abstract
This study evaluates the efficacy and safety of autologous serum eye drops (ASEDs) combined with sodium hyaluronate in treating dry eye disease (DED) after phacoemulsification cataract surgery. This retrospective cohort study included patients diagnosed with DED within 1 week to 1 month after cataract surgery at our hospital (August 2022–July 2023). Patients were divided into a combined group (ASEDs + sodium hyaluronate, n = 48) and a monotherapy group (sodium hyaluronate only, n = 63). Propensity score matching was used to balance baseline characteristics, resulting in 48 patients in each group. Both groups were treated for at least 4 weeks. Clinical indicators, including Ocular Surface Disease Index (OSDI), Schirmer I test (SIT), tear breakup time (BUT), fluorescein staining, conjunctival hyperemia, and conjunctival impression cytology, were assessed before and after treatment. After propensity score matching, baseline characteristics were comparable (P > .05). The mean age was 43.83 ± 8.84 years in the combined group and 43.93 ± 8.84 years in the monotherapy group (P = .865), with male proportions of 47.9% and 45.8%, respectively (P = .779). Other variables, including body mass index, disease duration, OSDI, SIT, and BUT, also showed no significant differences. After 4 weeks, the combined group showed significantly greater improvements. OSDI scores decreased to 14.09 ± 4.22 versus 21.50 ± 4.82 (P < .001); SIT increased to 10.23 ± 2.00 mm versus 8.50 ± 1.50 mm (P < .001); BUT extended to 8.18 ± 0.96 seconds versus 6.00 ± 1.00 seconds (P < .001). Fluorescein staining scores reduced to 0.56 ± 0.22 versus 1.86 ± 0.76 (P < .001), with conjunctival hyperemia and conjunctival impression cytology scores also significantly improved in the combined group (P < .001). ASEDs combined with sodium hyaluronate significantly improve both symptoms and ocular surface parameters in post-cataract DED patients, showing superior efficacy over monotherapy and promising clinical value.
Keywords: autologous serum, cataract extraction, corneal diseases, dry eye syndromes, sodium hyaluronate, tear film
1. Introduction
Cataract is the leading cause of reversible blindness worldwide, characterized by the gradual clouding of the lens, resulting in visual impairment.[1,2] Cataracts primarily occur in the elderly population. As the disease progresses, patients often experience symptoms such as decreased vision, photophobia, monocular diplopia, and glare sensitivity, which severely affect their quality of life and daily functioning.[3] Currently, phacoemulsification combined with intraocular lens implantation is the standard clinical treatment for cataracts.[4] This surgical procedure can effectively restore visual function with confirmed efficacy. However, postoperative complications may still arise during the surgery, among which dry eye disease (DED) is relatively common. DED can negatively impact postoperative visual quality and patient satisfaction.
The incidence of DED after cataract surgery is relatively high, with literature reports indicating a rate ranging from 9.8% to 33%. It is more commonly observed in elderly patients and those with unstable ocular surface conditions.[5] The pathogenesis of postoperative DED is complex and mainly involves factors such as corneal nerve damage caused by surgical incisions, chronic ocular surface inflammation, disruption of the tear film structure, and prolonged exposure to intraoperative microscopic light sources and irrigation fluids.[6] These factors contribute to reduced tear secretion, decreased tear film stability, increased tear evaporation, and damage to the ocular surface epithelium, ultimately triggering or exacerbating DED. Patients often experience symptoms such as ocular dryness, foreign body sensation, burning sensation, visual fatigue, and blurred vision. Without timely intervention, postoperative DED can delay ocular surface healing, affect postoperative visual recovery, and reduce patient satisfaction after surgery.[7]
At present, the treatment of postoperative DED mainly relies on artificial tears, among which sodium hyaluronate eye drops are the most widely used.[8] Sodium hyaluronate is a high molecular weight glycosaminoglycan composed of alternating N-acetylglucosamine and glucuronic acid units. It has excellent water retention and viscoelastic properties, allowing it to form a protective film on the ocular surface, reduce friction between the eyelid and the cornea, maintain tear film moisture, and enhance tear film stability. Although sodium hyaluronate eye drops are effective in alleviating dry eye symptoms, their single use still has certain limitations in promoting corneal repair and restoring ocular surface homeostasis in patients with moderate to severe DED.[9]
In recent years, autologous serum eye drops (ASEDs) have gradually become an important treatment option for DED, especially in patients with refractory dry eye.[10] ASEDs closely resemble natural tears in composition and are rich in various bioactive components, such as epidermal growth factor, nerve growth factor, transforming growth factor-beta, fibronectin, vitamin A, and immunoglobulins.[11] These active factors play key roles in promoting the proliferation and differentiation of corneal and conjunctival epithelial cells, alleviating ocular surface inflammation, and facilitating the regeneration of ocular surface tissues.[12] However, existing research on the application of ASEDs in postoperative DED following cataract surgery remains limited. Furthermore, studies on the efficacy and safety of combining ASEDs with sodium hyaluronate eye drops are still scarce.
Therefore, the aim of this study is to investigate the clinical efficacy and safety of ASEDs combined with sodium hyaluronate eye drops in the treatment of DED after cataract surgery. We hypothesize that the combination therapy, compared to sodium hyaluronate eye drops alone, can more effectively improve both subjective symptoms and objective clinical indicators in patients with postoperative DED. To minimize the impact of potential confounding factors on the study results, we adopted the propensity score matching (PSM) method, providing a reference for optimizing clinical treatment strategies for postoperative DED following cataract surgery.
2. Research methods
2.1. Study design
This study was approved by the Ethics Committee of the First People’s Hospital of Linping District. This study is a retrospective cohort study aimed at evaluating the clinical efficacy and safety of ASEDs combined with sodium hyaluronate eye drops in patients with DED after cataract surgery. Medical records of patients who developed DED following phacoemulsification cataract surgery in the Department of Ophthalmology at our hospital between August 2022 and July 2023 were retrospectively collected. As this was a retrospective study, formal informed consent was waived by the hospital’s ethics committee. However, all patients had been clearly informed of and agreed to their treatment plans at the time of care.
Based on the postoperative dry eye treatment they received, patients were divided into 2 groups: combination therapy group: treated with ASEDs combined with sodium hyaluronate eye drops (48 patients). Monotherapy group: treated with sodium hyaluronate eye drops alone (63 patients). Both groups received standard postoperative cataract care and routine medications (such as anti-inflammatory and anti-infective drugs). The treatment for DED lasted no less than 4 weeks. To control for baseline differences between groups, the PSM method was applied, and ultimately, 48 patients were included in each group for analysis.
Inclusion criteria
Patients aged ≥ 18 years, regardless of gender, who underwent phacoemulsification cataract surgery at our hospital and developed DED within 1 week to 1 month postoperatively, meeting the diagnostic criteria outlined in the Expert Consensus on Clinical Diagnosis and Treatment of Dry Eye (2020).[13] Diagnosis required at least 2 of the following: (1) dry eye symptoms (e.g., dryness, burning, blurred vision); (2) Schirmer I test (SIT) ≤ 10 mm/5 minutes; (3) tear film breakup time (BUT) ≤ 10 seconds; (4) positive fluorescein staining (FL). Included patients had no history of preoperative DED, no severe postoperative ocular complications, and complete clinical and follow-up data. Patients in the combination group used both autologous serum and sodium hyaluronate eye drops; those in the control group used sodium hyaluronate alone.
Exclusion criteria
Preoperative DED or chronic dry eye symptoms.
Other ocular conditions affecting assessment (e.g., keratitis, ulcers, trauma, severe malformations).
Systemic diseases affecting tear secretion or autologous serum safety (e.g., autoimmune disorders, anemia, hepatitis B/C, HIV/AIDS, sepsis).
Severe systemic illnesses (e.g., cardiovascular, pulmonary, renal, hepatic, or gastrointestinal disorders).
Recent surgeries (e.g., <2 weeks after minor, <3 months after abdominal, <6 months after major organ surgeries).
Malignancies, pregnancy/lactation, frailty, or blood-draw intolerance.
Poor treatment compliance or incomplete follow-up.
2.2. Treatment methods
2.2.1. Monotherapy group
Patients in the monotherapy group received standardized postoperative care following phacoemulsification cataract surgery. This included the routine use of postoperative antibiotic eye drops and corticosteroid eye drops to prevent infection and control postoperative inflammatory responses. On this basis, patients in the monotherapy group were treated solely with sodium hyaluronate eye drops (Trade name: Hylash®; Specification: 0.1%) to alleviate dry eye symptoms.
The administration of sodium hyaluronate eye drops was as follows: initiation time: within 1 week after surgery. Dosage frequency: 4 times daily: morning, noon, evening, and before bedtime. Dosage per application: 1 drop each time, administered to both eyes. Treatment duration: continuous use for at least 4 weeks.
During the treatment period, patients underwent standardized follow-up management to observe improvements in dry eye symptoms and monitor for adverse reactions. Throughout treatment, all patients adhered to aseptic procedures. The dropper tip of the eye drop bottle was not allowed to touch the eyelashes or ocular surface to avoid cross-contamination. If ocular infections or other adverse reactions occurred, medication was discontinued promptly and appropriate management was provided.
2.3. Combination therapy group
2.3.1. Preparation and management of ASEDs[14]
Preparation before collection: strict adherence to aseptic principles was maintained. Prior to blood collection, clinical physicians conducted a detailed medical history inquiry to exclude systemic and ocular contraindications. Informed consent was obtained from all patients. Routine pre-collection screening was performed for serum pathogens (hepatitis B virus, hepatitis C virus, human immunodeficiency virus, Treponema pallidum, and human T-cell lymphotropic virus) and basic laboratory parameters (complete blood count, C-reactive protein, serum amyloid A, alanine aminotransferase, rheumatoid factor, anti-streptolysin O) to rule out blood-borne infectious diseases and other contraindications.
Blood collection: the cubital vein puncture area was disinfected 2 to 3 times using standard procedures. A volume of 25 to 100 mL of venous blood was collected. Among this, 10 mL was used for pathogen and baseline parameter testing. The remaining blood was placed in sterile vacuum blood collection tubes without anticoagulants and left to clot at room temperature for 2 hours.
Centrifugation and dilution: after coagulation was complete, samples were centrifuged at 3000 rpm for 10 minutes. The serum supernatant was extracted under a biosafety cabinet using sterile syringes and diluted with 0.9% sodium chloride injection to achieve a concentration of 20% or 50%.
Aliquoting and testing: the diluted serum was dispensed into sterile ophthalmic eye drop bottles at 1 mL per bottle. Labels were attached to indicate the patient’s name, gender, age, preparation date, preparer’s name, and expiration date. After dispensing, a 48-hour microbial culture was performed. Bottles with negative results were approved for use; bottles with positive results were discarded. Upon dispensing, patients were instructed on aseptic handling techniques and informed that the drops were for their personal use only to avoid contamination and cross-infection.
Storage: after preparation, the serum eye drops were stored protected from light. They were refrigerated at 4 °C for no longer than 1 week or frozen at −20 °C for no longer than 3 months. Frozen drops were thawed at 4 °C before use and could not be refrozen after thawing. Opened bottles had to be used within 24 hours, and any remaining solution was discarded.
2.3.2. Administration of ASEDs
The eye drops were instilled once every 2 hours. Drops were applied with the bottle held in suspension, ensuring that the dropper tip did not come into contact with the eyelashes or eyelids. Once opened, the eye drop bottle should not be used overnight. If the serum exhibited abnormal color or turbidity, use was to be discontinued immediately and the bottle discarded.
During the treatment period, the following conditions required cessation of use and appropriate evaluation and management: allergic reactions or signs of infection; eyelid skin eczema; anemia resulting from frequent blood draws.
Sodium hyaluronate eye drops were used alternately with ASEDs, with an interval of no <30 minutes between the 2. Autologous serum eye drops were administered first.
3. Data collection
3.1. General patient information
General information was obtained through the electronic medical record system and follow-up records. The collected data included: age, gender, body mass index (BMI), education level (grouped as junior high school or below), duration of cataract disease (years), history of hypertension, history of diabetes, laterality of surgery (unilateral/bilateral), duration of cataract surgery (minutes), postoperative corticosteroid use, and medication compliance assessment. All baseline data were entered and verified by trained professionals to ensure completeness and accuracy. Only patients who completed the full 4-week treatment and follow-up assessments were included in the analysis to ensure treatment compliance and data validity.
3.2. Ocular Surface Disease Index (OSDI) score[15]
To assess the severity of subjective symptoms in patients with DED, the OSDI questionnaire was used. This questionnaire consists of 12 items covering visual function impairment, ocular discomfort symptoms, and environmental trigger effects. The total score ranges from 0 to 100, with higher scores indicating more severe dry eye symptoms. All patients were required to complete the questionnaire before treatment and after 4 weeks of treatment. Trained evaluators provided on-site guidance during completion to ensure standardization of the assessment process.
3.3. Fluorescein BUT (FBUT)[16]
FBUT testing was conducted under room temperature, appropriate humidity, and light-shielded conditions. A sterile dropper was used to instill 2 μL of 1% fluorescein sodium solution into the patient’s lower conjunctival sac, or fluorescein test paper moistened with antibiotic eye drops was gently touched to the lower eyelid margin. After the patient blinked naturally 3 to 4 times, they were instructed to look straight ahead. Tear film stability was observed under a slit lamp using cobalt blue light. The time from the last blink to the first appearance of a black spot on the cornea was recorded. The test was repeated 3 times, and the average value was taken as the final result. A BUT ≤ 10 seconds indicates reduced tear film stability.
3.4. Schirmer I test (SIT)[17]
Tear secretion function was assessed using the SIT, performed without topical anesthesia. Standard filter paper strips (5 × 35 mm) were folded 5 mm from 1 end and placed at the outer third of the lower conjunctival sac. After the patient closed their eyes and sat quietly for 5 minutes, the strips were removed, and the length of the wetted area (mm) was measured. Each eye was measured 3 times, and the average value was recorded as the final result. A wetting length ≥ 10 mm/5 minutes is considered normal, while ≤ 10 mm/5 minutes indicates abnormal tear secretion function.
3.5. Corneal–conjunctival FL[18]
Corneal and conjunctival FL was evaluated under a slit lamp using cobalt blue light. After staining with 1% fluorescein sodium, the Oxford grading scheme was used for scoring. Scores were assigned based on the distribution and density of staining points, with a total score range of 0 to 15 points. Higher scores indicate more severe epithelial damage of the cornea and conjunctiva. Each patient was examined both before and after treatment, and all evaluations were performed by the same group of physicians to ensure consistency.
3.6. Conjunctival hyperemia score
The degree of conjunctival hyperemia was assessed by slit lamp microscopy. Scoring was categorized into 4 grades: no hyperemia (0 points), mild hyperemia (1 point), moderate hyperemia (2 points), and severe hyperemia (3 points). All scores were independently determined by 2 experienced ophthalmologists in a double-blind manner, and the average value was used as the final score.
3.7. Conjunctival impression cytology (CIC) score[19]
CIC samples were collected using cellulose acetate filter paper. After PAS and HE staining, conjunctival epithelial cells and goblet cells were observed under a light microscope at 400× magnification. Scoring was based on the Nelson (1989) criteria:
Grade 0: normal conjunctival epithelial cells with densely distributed goblet cells.
Grade 1: mild enlargement of conjunctival epithelial cells with a reduction in goblet cells.
Grade 2: marked enlargement and flattening of conjunctival epithelial cells with sparse goblet cells.
Grade 3: enhanced cytoplasmic staining of conjunctival epithelial cells, obvious keratinization, and absence of goblet cells.
For each patient, 3 high-power fields were counted, and the average value was used as the final score.
3.8. Statistical analysis
All data were analyzed using SPSS 26.0 statistical software. Measurement data were tested for normality and expressed as mean ± standard deviation (mean ± SD). Between-group comparisons were performed using independent sample t tests, while within-group comparisons before and after treatment were conducted using paired t tests. Categorical data were expressed as case numbers (n), and between-group comparisons were performed using the χ² test or Fisher exact test. Missing data accounted for <5% of the total dataset and were handled using multiple imputation to reduce bias and preserve statistical power. To control for the impact of baseline differences, the PSM method was applied, with a matching ratio of 1:1 and a caliper width of 0.2. Matching variables included age, gender, BMI, disease duration, education level, underlying diseases, and dry eye-related clinical indicators. All statistical tests were two-sided, and a P value < .05 was considered statistically significant.
3. Results
3.1. Baseline characteristics before and after PSM
To reduce confounding and improve comparability between groups, PSM was performed. Before matching, significant differences were observed in several baseline variables (e.g., age, gender, BMI, disease duration, OSDI, BUT, SIT, FL score, and comorbidities) (all P < .05; Table 1). After 1:1 matching, 48 patients were included in each group with no statistically significant differences in key characteristics (all P > .05).
Table 1.
Baseline characteristics before and after propensity score matching.
| Covariates | Before matching | P value | After matching | P value | ||
|---|---|---|---|---|---|---|
| Combined treatment group (n = 48) | Before matching monotherapy group (n = 63) | Combined treatment group (n = 48) | Monotherapy group (n = 48) | |||
| Age (yr) | 43.8 ± 8.8 | 41.8 ± 9.8 | .032 | 43.8 ± 8.8 | 43.9 ± 8.8 | .865 |
| Male (n) | 23 | 24 | .045 | 23 | 22 | .779 |
| Body mass index (BMI, kg/m²) | 20.3 ± 0.8 | 21.3 ± 1.3 | .028 | 20.3 ± 0.8 | 20.3 ± 0.8 | .902 |
| Disease duration (yr) | 3.1 ± 0.9 | 4.1 ± 1.4 | .04 | 3.1 ± 0.9 | 3.2 ± 0.9 | .815 |
| Education (below junior high school, n) | 10 | 23 | .015 | 10 | 10 | .942 |
| Ocular Surface Disease Index (OSDI) | 39.1 ± 11.7 | 50.1 ± 7.1 | .012 | 39.1 ± 11.7 | 40.7 ± 6.1 | .976 |
| Tear break-up time (BUT, sec) | 2.9 ± 1.4 | 3.6 ± 1.0 | .005 | 2.9 ± 1.4 | 2.9 ± 0.8 | .888 |
| Schirmer I test (mm) | 4.9 ± 1.7 | 5.1 ± 1.4 | .038 | 4.9 ± 1.7 | 4.8 ± 1.1 | .965 |
| Fluorescein staining score | 4.5 ± 1.4 | 3.0 ± 0.9 | .001 | 4.5 ± 1.4 | 4.2 ± 0.8 | .916 |
| Hypertension (n) | 10 | 18 | .02 | 10 | 10 | .912 |
| Diabetes mellitus (n) | 8 | 14 | .05 | 8 | 8 | .985 |
| Bilateral surgery (n) | 31 | 44 | .047 | 31 | 32 | .974 |
| Surgical duration (min) | 35.2 ± 8.3 | 40.1 ± 10.5 | .048 | 35.5 ± 8.4 | 35.8 ± 8.5 | .945 |
| Postoperative corticosteroid use (n) | 48 | 63 | 1 | 48 | 48 | 1 |
| Medication compliance (good, n) | 41 | 49 | .025 | 41 | 40 | .962 |
Specifically, the mean age was 43.83 ± 8.84 years in the combination group and 43.93 ± 8.84 years in the monotherapy group (P = .865), with male patients accounting for 47.9% and 45.8%, respectively (P = .779). BMI, OSDI, SIT, BUT, and the proportions of bilateral surgery, hypertension, and diabetes were also well balanced. These results confirm that PSM effectively minimized baseline differences, enhancing the reliability of subsequent treatment effect comparisons.
4.2. Improvement of dry eye symptoms (OSDI score) in the combination therapy group and monotherapy group
To evaluate the improvement of subjective symptoms in patients with DED, this study compared the changes in OSDI scores between the combination therapy group and the monotherapy group before and after treatment. Before treatment, there was no statistically significant difference in OSDI scores between the 2 groups, as shown in Table 2. After treatment, both groups showed significant improvement compared to before treatment.
Table 2.
Comparison of Ocular Surface Disease Index (OSDI) scores before and after treatment between the combined treatment group and monotherapy group.
| Group | OSDI before treatment (mean ± SD) | OSDI after treatment (mean ± SD) | T value | P value |
|---|---|---|---|---|
| Combined treatment | 39.06 ± 11.66 | 14.09 ± 4.22 | 20.9 | .000 |
| Monotherapy | 40.70 ± 6.10 | 21.50 ± 4.82 | 16.75 | .000 |
| T value | -0.82 | -8.02 | ||
| P value | .415 | .000 |
In the combination therapy group, the OSDI score decreased from 39.06 ± 11.66 points before treatment to 14.09 ± 4.22 points after treatment, with a statistically significant difference (T = 20.90, P = .000). In the monotherapy group, the OSDI score decreased from 40.70 ± 6.10 points before treatment to 21.50 ± 4.82 points after treatment, also showing a statistically significant difference (T = 16.75, P = .000).
In addition, the post-treatment OSDI score of the combination therapy group was significantly lower than that of the monotherapy group (14.09 ± 4.22 points vs 21.50 ± 4.82 points), and the difference between groups was statistically significant (T = −8.02, P = .000). The results suggest that combination therapy is superior to monotherapy in alleviating the subjective symptoms of patients with DED.
4.3. Improvement of tear secretion function (SIT) in the combination therapy group and monotherapy group
To evaluate the effect of different treatment regimens on tear secretion function in patients with DED after cataract surgery, this study compared the changes in SIT results between the combination therapy group and the monotherapy group before and after treatment, as shown in Table 3.
Table 3.
Comparison of Schirmer I test (SIT) results before and after treatment between the combined treatment group and monotherapy group.
| Group | SIT before treatment (mean ± SD) | SIT after treatment (mean ± SD) | T value | P value |
|---|---|---|---|---|
| Combined treatment | 4.92 ± 1.76 | 10.23 ± 2.00 | 18.34 | .000 |
| Monotherapy | 4.81 ± 1.12 | 8.50 ± 1.50 | 15.02 | .000 |
| T value | 0.316 | 4.580 | ||
| P value | .752 | .000 |
Before treatment, there was no statistically significant difference in SIT results between the combination therapy group and the monotherapy group (T = 0.316, P = .752), indicating comparability at baseline. After treatment, SIT results in both groups were significantly higher than before treatment. In the combination therapy group, SIT increased from 4.92 ± 1.76 mm to 10.23 ± 2.00 mm (T = 18.34, P = .000); in the monotherapy group, SIT increased from 4.81 ± 1.12 mm to 8.50 ± 1.50 mm (T = 15.02, P = .000), and the differences were statistically significant in both groups.
In addition, the SIT result in the combination therapy group after treatment was significantly better than that in the monotherapy group (10.23 ± 2.00 mm vs 8.50 ± 1.50 mm), and the difference between groups was statistically significant (T = 4.580, P = .000).
4.4. Improvement of tear film stability (BUT) in the combination therapy group and monotherapy group
To evaluate the effect of different treatment methods on tear film stability in patients with DED after cataract surgery, this study compared the changes in tear film BUT between the combination therapy group and the monotherapy group before and after treatment, as shown in Table 4. Before treatment, the BUT results of the 2 groups were 2.89 ± 1.42 seconds in the combination therapy group and 2.91 ± 0.80 seconds in the monotherapy group. There was no statistically significant difference between the 2 groups (T = -0.08, P = .935), indicating comparability at baseline. After treatment, the BUT of both groups was significantly prolonged compared to before treatment. In the combination therapy group, BUT increased from 2.89 ± 1.42 seconds to 8.18 ± 0.96 seconds (T = 22.05, P = .000); in the monotherapy group, BUT increased from 2.91 ± 0.80 seconds to 6.00 ± 1.00 seconds (T = 17.50, P = .000), and the differences were statistically significant in both groups.
Table 4.
Comparison of tear break-up time (BUT) before and after treatment between the combined treatment group and monotherapy group.
| Group | BUT before treatment (Mean ± SD) | BUT after treatment (Mean ± SD) | T value | P value |
|---|---|---|---|---|
| Combined treatment | 2.89 ± 1.42 | 8.18 ± 0.96 | 22.05 | .000 |
| Monotherapy | 2.91 ± 0.8 | 6.0 ± 1.0 | 17.5 | .000 |
| T value | -0.08 | 8.65 | ||
| P value | .935 | .000 |
Further comparison of BUT between the 2 groups after treatment showed that the combination therapy group was significantly better than the monotherapy group (8.18 ± 0.96 seconds vs 6.00 ± 1.00 seconds), and the difference was statistically significant (T = 8.65, P = .000).
4.5. Improvement of corneal–conjunctival FL score in the combination therapy group and monotherapy group
To evaluate the improvement effect of different treatment regimens on corneal–conjunctival damage in patients with DED after cataract surgery, this study compared the changes in corneal–conjunctival FL scores between the combination therapy group and the monotherapy group before and after treatment, as shown in Table 5.
Table 5.
Improvement in corneal and conjunctival fluorescein staining (FL) scores between the combined treatment group and monotherapy group.
| Group | FL before treatment (mean ± SD) | FL after treatment (mean ± SD) | T value | P value |
|---|---|---|---|---|
| Combined treatment | 4.47 ± 1.43 | 0.56 ± 0.22 | 25.8 | 0 |
| Monotherapy | 4.20 ± 0.79 | 1.86 ± 0.76 | 18.15 | 0 |
| T value | 1.25 | -11.37 | ||
| P value | .215 | 0 |
Before treatment, the FL scores of the 2 groups were 4.47 ± 1.43 points in the combination therapy group and 4.20 ± 0.79 points in the monotherapy group. There was no statistically significant difference between the 2 groups (T = 1.25, P = .215), indicating comparability in baseline data. After treatment, the FL scores in both groups were significantly lower than before treatment. In the combination therapy group, the FL score decreased from 4.47 ± 1.43 points to 0.56 ± 0.22 points, with a statistically significant difference (T = 25.80, P = .000); in the monotherapy group, the FL score decreased from 4.20 ± 0.79 points to 1.86 ± 0.76 points, also showing a statistically significant difference (T = 18.15, P = .000).
Further comparison of the FL scores between the 2 groups after treatment showed that the combination therapy group had significantly lower scores than the monotherapy group (0.56 ± 0.22 points vs 1.86 ± 0.76 points), and the difference was statistically significant (T = −11.37, P = .000).
4.6. Improvement of conjunctival hyperemia score in the combination therapy group and monotherapy group
To further evaluate the improvement of ocular surface hyperemia symptoms in patients with DED after cataract surgery, this study compared the changes in conjunctival hyperemia scores between the combination therapy group and the monotherapy group before and after treatment. Before treatment, the conjunctival hyperemia scores were 2.5 ± 0.5 points in the combination therapy group and 2.4 ± 0.5 points in the monotherapy group. There was no statistically significant difference between the 2 groups (T = 0.85, P = .400), indicating comparability at baseline. After treatment, the conjunctival hyperemia scores in both groups were significantly reduced. In the combination therapy group, the score decreased from 2.5 ± 0.5 points to 0.8 ± 0.4 points, with a statistically significant difference (T = 20.35, P = .000); in the monotherapy group, the score decreased from 2.4 ± 0.5 points to 1.5 ± 0.5 points, also showing a statistically significant difference (T = 15.10, P = .000), as shown in Table 6.
Table 6.
Comparison of conjunctival hyperemia scores before and after treatment between the combined treatment group and monotherapy group.
| Group | Hyperemia score before treatment (mean ± SD) | Hyperemia score after treatment (mean ± SD) | T value | P value |
|---|---|---|---|---|
| Combined Treatment | 2.5 ± 0.5 | 0.8 ± 0.4 | 20.35 | 0 |
| Monotherapy | 2.4 ± 0.5 | 1.5 ± 0.5 | 15.1 | 0 |
| T value | 0.85 | -7.5 | ||
| P value | .4 | 0 |
Further comparison of conjunctival hyperemia scores after treatment showed that the combination therapy group was significantly lower than the monotherapy group (0.8 ± 0.4 points vs 1.5 ± 0.5 points), and the difference was statistically significant (T = −7.50, P = .000).
4.7. Improvement of CIC score in the combination therapy group and monotherapy group
To evaluate the effect of different treatment methods on conjunctival epithelial cells and goblet cell changes in patients with DED after cataract surgery, this study compared the changes in conjunctival impression cytology (CIC) scores between the combination therapy group and the monotherapy group before and after treatment. Before treatment, there was no statistically significant difference in CIC scores between the combination therapy group and the monotherapy group (T = 0.83, P = .410). After treatment, the CIC scores of both groups were significantly lower than before treatment. In the combination therapy group, the CIC score decreased from 2.3 ± 0.6 points to 0.9 ± 0.5 points, with a statistically significant difference (T = 18.75, P = .000); in the monotherapy group, the CIC score decreased from 2.2 ± 0.5 points to 1.5 ± 0.5 points, also showing a statistically significant difference (T = 14.60, P = .000), as shown in Table 7.
Table 7.
Comparison of conjunctival impression cytology (CIC) scores before and after treatment between the combined treatment group and monotherapy group.
| Group | CIC score before treatment (mean ± SD) | CIC score after treatment (mean ± SD) | T value | P value |
|---|---|---|---|---|
| Combined treatment | 2.3 ± 0.6 | 0.9 ± 0.5 | 18.75 | 0 |
| Monotherapy | 2.2 ± 0.5 | 1.5 ± 0.5 | 14.6 | 0 |
| T value | 0.83 | -6 | ||
| P value | .41 | 0 |
Further comparison of CIC scores after treatment showed that the combination therapy group was significantly lower than the monotherapy group (0.9 ± 0.5 points vs 1.5 ± 0.5 points), and the difference was statistically significant (T = −6.00, P = .000).
5. Discussion
Cataract is a common visual impairment disease caused by lens opacification, predominantly affecting middle-aged and elderly populations. As the disease progresses, patients often experience symptoms such as decreased visual acuity, photophobia, and monocular diplopia, which severely affect their quality of life and daily functioning.[20] Phacoemulsification is commonly used in clinical practice to treat cataracts; however, some patients develop DED postoperatively. The effect of monotherapy in addressing postoperative DED is often limited. Therefore, selecting an appropriate postoperative treatment regimen is particularly important.
In this study, baseline differences were controlled using the PSM method to evaluate the clinical efficacy and safety of ASEDs combined with sodium hyaluronate eye drops in patients with DED after cataract surgery. The results showed that combination therapy was superior to sodium hyaluronate monotherapy in improving both subjective symptoms and objective clinical indicators of DED.
The findings demonstrated that combination therapy can significantly alleviate ocular discomfort symptoms in patients. After 4 weeks of treatment, the OSDI score in the combination therapy group was significantly lower than that in the monotherapy group (14.09 ± 4.22 vs 21.50 ± 4.82, P = .000). As a widely used subjective symptom scale for assessing DED, OSDI effectively reflects patients’ visual function impairment, ocular discomfort symptoms, and the impact of environmental factors.[21] These results suggest that ASEDs combined with sodium hyaluronate eye drops are more effective in alleviating subjective symptoms in patients with postoperative DED after cataract surgery.
In addition, the combination therapy also demonstrated significant advantages in tear secretion function and tear film stability. The SIT value in the combination therapy group increased from 4.92 ± 1.76 mm before treatment to 10.23 ± 2.00 mm, which was significantly better than that in the monotherapy group (8.50 ± 1.50 mm, P = .000). Regarding tear film breakup time (BUT), the combination therapy group showed a significant extension from 2.89 ± 1.42 seconds to 8.18 ± 0.96 seconds, also superior to the monotherapy group’s result of 6.00 ± 1.00 seconds (P = .000). These results are consistent with previous studies, further confirming that ASEDs, rich in growth factors such as epidermal growth factor, nerve growth factor, transforming growth factor-β, and vitamin A, have a composition similar to natural tears. These components promote lacrimal gland function recovery, epithelial repair, and maintenance of tear film stability.[22]
In terms of repairing corneal–conjunctival epithelial damage, this study showed that the corneal–conjunctival FL score in the combination therapy group was significantly lower than that in the monotherapy group (0.56 ± 0.22 vs 1.86 ± 0.76, P = .000), indicating better efficacy in promoting corneal–conjunctival epithelial healing. At the same time, the conjunctival hyperemia score and CIC score also showed greater improvements in the combination therapy group, suggesting that combination therapy can more effectively reduce ocular surface inflammation and promote goblet cell function recovery.[23] Specifically, the CIC score in the combination therapy group decreased from 2.3 ± 0.6 points before treatment to 0.9 ± 0.5 points after treatment, while in the monotherapy group, it only decreased to 1.5 ± 0.5 points (P = .000). These results further confirm that ASEDs play a role in repairing ocular surface epithelium, improving the ocular surface microenvironment, and modulating local immunity.
The mechanism of action of ASEDs mainly includes providing active substances similar to natural tears to promote corneal–conjunctival epithelial cell repair, regulate immune responses, alleviate ocular surface inflammation, and enhance tear film stability.[24] Sodium hyaluronate, with its excellent moisturizing and viscoelastic properties, increases tear film stability, reduces tear evaporation, and provides lubrication and protection to the ocular surface.[25] The combination of the 2 provides a synergistic effect in the treatment of DED, achieving comprehensive improvement in ocular surface function through multi-targeted intervention.
Despite the positive results, this study has several limitations. First, as a single-center retrospective study, even though PSM was used to reduce confounding, it cannot fully replace the rigor of randomization in prospective studies. PSM only adjusts for observed variables; unmeasured confounders: such as environmental factors, patient compliance, and subtle surgical variations: may still have influenced outcomes. Second, the sample size was relatively small after matching (n = 48 per group), limiting statistical power and precluding subgroup analyses. Third, the follow-up period was only 4 weeks, providing limited insight into the long-term efficacy and safety of the treatment. Future prospective, multi-center randomized trials with larger samples and extended follow-up are needed to validate these findings and address residual confounding. In addition, the standardization of the collection, preparation, dilution, storage, and application processes for ASEDs has not yet been unified. Variations exist among different studies and clinical practices, limiting the standardization and promotion of its clinical application. Future studies should conduct prospective, randomized controlled trials with multi-center, large-sample, and long-term follow-up designs to verify the efficacy and safety of ASEDs combined with sodium hyaluronate eye drops in the treatment of postoperative DED after cataract surgery. Furthermore, more in-depth exploration of the molecular mechanisms of ASEDs is needed, such as their effects on lacrimal gland function restoration, ocular surface immune regulation, and inflammatory factor expression. In addition, standardized preparation processes and clinical application guidelines should be established to enhance the quality and safety of ASEDs and promote their standardized and widespread clinical use. Multi-modal interventions, including meibomian gland function treatments, photodynamic therapy, and immunomodulatory drugs, could also be considered to achieve better therapeutic outcomes, comprehensively improving the management of postoperative DED after cataract surgery and enhancing patients’ quality of life.
In conclusion, the results of this study indicate that ASEDs combined with sodium hyaluronate eye drops have better clinical efficacy in patients with DED after cataract surgery. They can effectively relieve dry eye symptoms, promote tear secretion, improve tear film stability, repair ocular surface damage, and reduce inflammatory responses, showing promising prospects for clinical application.
Author contributions
Conceptualization: Lei Jiang, Yifeng Wu, Fangli Fan.
Data curation: Lei Jiang, Yifeng Wu, Zhen Deng.
Formal analysis: Lei Jiang, Yifeng Wu, Xujie Shu.
Validation: Zhen Deng.
Visualization: Zhen Deng.
Writing – original draft: Lei Jiang, Yifeng Wu, Xujie Shu, Fangli Fan, Zhen Deng.
Writing – review & editing: Lei Jiang, Yifeng Wu, Zhen Deng.
Abbreviations:
- ASEDs
- autologous serum eye drops
- BMI
- body mass index
- BUT
- tear breakup time
- CIC
- conjunctival impression cytology
- DED
- dry eye disease
- FL
- fluorescein staining
- OSDI
- Ocular Surface Disease Index
- PSM
- propensity score matching
- SIT
- Schirmer I test
The authors have no funding and conflicts of interest to disclose.
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
How to cite this article: Jiang L, Wu Y, Shu X, Fan F, Deng Z. The effect of autologous serum eye drops combined with sodium hyaluronate eye drops in the treatment of dry eye syndrome after cataract surgery. Medicine 2025;104:33(e43833).
Contributor Information
Lei Jiang, Email: 15372002998@163.com.
Yifeng Wu, Email: yundao911@126.com.
Xujie Shu, Email: 442736661@qq.com.
Fangli Fan, Email: ffl61719@163.com.
References
- [1].Asbell PA, Dualan I, Mindel J, Brocks D, Ahmad M, Epstein S. Age-related cataract. Lancet. 2005;365:599–609. [DOI] [PubMed] [Google Scholar]
- [2].Taylor A. Associations between nutrition and cataract. Nutr Rev. 1989;47:225–34. [DOI] [PubMed] [Google Scholar]
- [3].Do DV, Gichuhi S, Vedula SS, Hawkins BS. Surgery for postvitrectomy cataract. Cochrane Database Syst Rev. 2018;1:CD006366. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [4].Morris D, Fraser SG, Gray C. Cataract surgery and quality of life implications. Clin Interv Aging. 2007;2:105–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [5].Moshirfar M, Mifflin M, Wong G, Chang JC. Cataract surgery following phakic intraocular lens implantation. Curr Opin Ophthalmol. 2010;21:39–44. [DOI] [PubMed] [Google Scholar]
- [6].Go JA, Mamalis CA, Khandelwal SS. Cataract surgery considerations for diabetic patients. Curr Diab Rep. 2021;21:67. [DOI] [PubMed] [Google Scholar]
- [7].Bhandari S, Chew EY. Cataract surgery and the risk of progression of macular degeneration. Curr Opin Ophthalmol. 2023;34:27–31. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [8].Calder IG, Smith VH. Hyaluronidase and sodium hyaluronate in cataract surgery. Br J Ophthalmol. 1986;70:418–20. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [9].Purgert RJ, Bala E. Cataract surgery in a patient with apparent sodium hyaluronate allergy. Can J Ophthalmol. 2019;54:e220–1. [DOI] [PubMed] [Google Scholar]
- [10].Schulze SD, Sekundo W, Kroll P. Autologous serum for the treatment of corneal epithelial abrasions in diabetic patients undergoing vitrectomy. Am J Ophthalmol. 2006;142:207–11. [DOI] [PubMed] [Google Scholar]
- [11].Vazirani J, Sridhar U, Gokhale N, Doddigarla VR, Sharma S, Basu S. Autologous serum eye drops in dry eye disease: preferred practice pattern guidelines. Indian J Ophthalmol. 2023;71:1357–63. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [12].Wang Y, Xiao C, Niu H, Li J, Rao H, Li J. Effects of autologous serum and artificial tears on corneal sensation and tear film stability in patients with mild to moderate xerophthalmia after cataract surgery. Int Ophthalmol. 2025;45:32. [DOI] [PubMed] [Google Scholar]
- [13].Holzer MP, Auffarth GU, Specht H, Kruse FE. Combination of transepithelial phototherapeutic keratectomy and autologous serum eyedrops for treatment of recurrent corneal erosions. J Cataract Refract Surg. 2005;31:1603–6. [DOI] [PubMed] [Google Scholar]
- [14].Balal S, Udoh A, Pappas Y, et al. The feasibility of finger prick autologous blood (FAB) as a novel treatment for severe dry eye disease (DED): protocol for a randomised controlled trial. BMJ Open. 2018;8:e026770. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [15].Li J, Liao Y, Zhang SY, et al. Effect of laughter exercise versus 0.1% sodium hyaluronic acid on ocular surface discomfort in dry eye disease: non-inferiority randomised controlled trial. BMJ. 2024;386:e080474. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [16].Remongin PE, Rousseau A, Best AL, et al. Place du NIBUT automatisé dans l’évaluation multimodale de la surface oculaire dans le syndrome sec avec le Lacrydiag [Multimodal evaluation of the ocular surface using a the new Lacrydiag device]. J Fr Ophtalmol. 2021;44:313–20. [DOI] [PubMed] [Google Scholar]
- [17].Huo Y, Huang X, Lin L, et al. The effect of intense pulsed light combined with topical 0.05% Cyclosporin A eyedrops in the treatment of Sjögren’s syndrome related dry eye. Expert Rev Clin Immunol. 2024;20:1261–7. [DOI] [PubMed] [Google Scholar]
- [18].Tauber J, Berdy GJ, Wirta DL, Krösser S, Vittitow JL. NOV03 for dry eye disease associated with meibomian gland dysfunction: results of the randomized phase 3 GOBI study. Ophthalmology. 2023;130:516–24. [DOI] [PubMed] [Google Scholar]
- [19].Weber SP, Hazarbassanov RM, Nasaré A, Gomes JAP, Hofling-Lima AL. Conjunctival impression cytology evaluation of patients with dry eye disease using scleral contact lenses. Cont Lens Anterior Eye. 2017;40:151–6. [DOI] [PubMed] [Google Scholar]
- [20].Thompson J, Lakhani N. Cataracts. Prim Care. 2015;42:409–23. [DOI] [PubMed] [Google Scholar]
- [21].Di Zazzo A, Coassin M, Micera A, et al. Ocular surface diabetic disease: a neurogenic condition? Ocul Surf. 2021;19:218–23. [DOI] [PubMed] [Google Scholar]
- [22].Young AL, Cheng AC, Ng HK, Cheng LL, Leung GY, Lam DS. The use of autologous serum tears in persistent corneal epithelial defects. Eye (Lond). 2004;18:609–14. [DOI] [PubMed] [Google Scholar]
- [23].Shtein RM, Shen JF, Kuo AN, Hammersmith KM, Li JY, Weikert MP. Autologous serum-based eye drops for treatment of ocular surface disease: a report by the American Academy of Ophthalmology. Ophthalmology. 2020;127:128–33. [DOI] [PubMed] [Google Scholar]
- [24].Pan Q, Angelina A, Marrone M, Stark WJ, Akpek EK. Autologous serum eye drops for dry eye. Cochrane Database Syst Rev. 2017;2:CD009327. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [25].Cui D, Li G, Akpek EK. Autologous serum eye drops for ocular surface disorders. Curr Opin Allergy Clin Immunol. 2021;21:493–9. [DOI] [PubMed] [Google Scholar]