The present prospective, randomized, controlled, double-blind clinical trial aimed to evaluate the efficacy and safety of early YAG laser vitreolysis in treating symptomatic vitreous floaters. The clinical trial is presently being undertaken at Dongyang People’s Hospital, China. Ethical approval was obtained from the institutional ethics committee at the Dongyang People's Hospital. Prior to enrollment, written informed consent was collected from the participants. The schedule for enrollment, intervention, data collection, and assessment was in accordance with the Standardized Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines (see Fig. 1). The study flow schedule is depicted in Fig. 2. We followed the SPIRIT reporting guidelines during the drafting of this article[15].
Participant eligibility
Inclusion criteria
Participants who have experienced symptomatic floaters for a duration of one month will be enrolled in the study. To be eligible for the study, the patient must rate their visual disturbance caused by floaters as at least 4 on a 0–10 scale, with 0 being no symptoms and 10 being debilitating symptoms. The symptomatic Weiss ring must be at least 2mm from the retina and 5mm from the posterior capsule of the crystalline lens, as measured on B-scan. There is no minimum required distance from the intraocular lens for patients who have had cataract surgery (pseudophakic patients). The patient must be able to position themselves for the YAG laser procedure and accept the risks associated with the procedure, including but not limited to retinal detachment, intraocular hemorrhage, retinal damage, cataract formation, optic nerve damage, inflammation, and irreversible loss of vision. Additionally, the patient must be willing and able to comply with clinic visits and study-related procedures. If the patient has symptoms in both eyes, only one eye can be included in the study and randomized.
Exclusion criteria
The exclusion criteria are as follows: History of a retinal detachment, retinal tear, or uveitis in the study eye. History of macular edema, diabetic retinopathy, retinal vein occlusion, or aphakia in the study eye. History of glaucoma or high intraocular pressure, defined as having undergone glaucoma surgery in the eye being studied, or currently using two or more topical glaucoma medications in the eye being studied.
Randomization and masking
In this study, a stratified randomization method will be used to allocate participants to two groups in a 1:1 ratio, using SPSS v26.0 (SPSS Inc, Chicago, IL, USA). A random allocation sequence will be created in advance and sealed in sequentially numbered opaque envelopes, allowing for randomization one at a time. Group allocation will be carried out by another researcher to ensure the randomization process is unbiased. All researchers involved in the study, including outcome assessors, statisticians, and data analysts, will be blinded to group assignment, but those providing the intervention will be informed as necessary. Prior to the trial, researchers will undergo comprehensive training in the randomization procedure and will be made aware of their individual responsibilities. The successful implementation and maintenance of the randomization and blinding method will be validated to ensure the reliability and lack of bias of the trial results.
The Investigator is strongly advised to uphold the blinding to the greatest extent possible. The actual allocation should not be revealed to the patient or any other study personnel, including site personnel, monitors, or project office staff. There should also be no written or verbal disclosure of the code in any of the patient-related documents associated with the study.
Recruitment
At Dongyang People's Hospital, more than 1,000 patients sought treatment for vitreous floaters annually, ensuring an ample pool of participants for our studies. Participants will be recruited by ophthalmologists during outpatient visits, without any additional advertising. Interested patients will be invited to discuss the study details with an ophthalmologist. Those who meet all the inclusion criteria will receive complete information regarding their responsibilities and all procedures involved in the trial. Prior to enrollment, they will be asked to sign a written informed consent form. Insurance coverage, provided for all trial participants, is contracted to compensate for any harm that may occur during the final study visit.
Intervention
YAG vitreolysis procedure
A Karickoff lens with goniosol will be used by the treating physician to perform YAG vitreolysis, with the number of shots determined based on clinical discretion. A focus offset may also be used if necessary, and the treatment will be conducted in single-shot mode with a maximum energy per pulse of 7 mJ. The endpoint of the treatment will be the vaporization of the Weiss ring into gas, as well as the fragmentation of any other vitreous opacities that are considered visually significant by the physician.
Sham laser procedure
The same procedure will be followed, but with the laser power turned down to 0.3 mJ and a separate lens covered by a filter that absorbs the power to ensure that no laser energy enters the eye.
Primary outcome
The study will measure the primary outcomes at 3, 6, 9, and 12 months. These outcomes include the subjective improvement in floater symptoms, which is rated on a scale of 0 to 10. A score of 0 represents no symptoms, while a score of 10 indicates symptoms that significantly impact daily life. The study also measures the mean change in the National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25), which is a self-reported questionnaire that evaluates a patient's visual function and its effect on their quality of life. The VFQ-25 consists of 25 items, which assess different domains of vision-related quality of life, including general vision, near and distance activities, driving, social functioning, and mental health. The minimum score for the VFQ-25 is 0, indicating the worst possible visual function and quality of life, while the maximum score is 100, representing the best possible visual function and quality of life. Higher scores on the VFQ-25 indicate better outcomes, indicating that the patient has improved visual function and quality of life.
Secondary outcome
The secondary outcomes of the study encompass the objective assessment of changes through OCT and fundus photography. The objective evaluation of vitreous floater improvement using OCT and fundus photography is categorized into five levels: worsening, no change, mild improvement, significant improvement, and complete improvement. The objective evaluation will be conducted at 3, 6, 9, and 12 months.
Other secondary outcomes include the incidence and severity of ocular and systemic adverse events, such as retinal tears, retinal hemorrhage, retinal detachment, lens damage, and other related adverse events. The incidence rates of these adverse events will be recorded immediately after each laser treatment and at 1-month post-treatment.
Sample size calculation
The sample size is determined a priori based on calculations assuming a modest improvement of 30% in symptoms in the YAG group compared to 10% in the sham group. This results in a sample of 66 patients with a standard deviation of 25%, an alpha level of 0.05, and a statistical power of 0.9. To account for a 5% rate of lost follow-up, it was decided to include 70 subjects in the study.
Data collection, management, and monitoring
Before the trials commence, all investigators undergo comprehensive training on the clinical trial protocol, data management, and indicator evaluation methodology. Throughout the study, investigators diligently collect and record data in the participants' medical records. All adverse events are carefully documented in the electronic case report form (CRF).
Participants who cannot be followed up for the entire study duration are considered as dropouts. Participants have the option to withdraw from the study voluntarily in cases of intolerable side effects or poor treatment efficacy. Additionally, participants can withdraw from the study at any time for any reason. The investigators have the authority to withdraw participants from the study to prioritize their safety.
Any modifications to the study protocol require prior approval from the institutional ethics committee at Dongyang People's Hospital. Once approved, these changes must be documented in the trial registry and subsequently included in the final research data report.
During the experiment, concurrent treatments such as chronic diabetes, hypertension, anxiolytics, and antidepressant drugs are accepted. After all the follow-ups, participants are asked about receiving any other interventions during the study period, and this information is reported with the study results.
To minimize data loss, all participants are provided with guidance when they sign the informed consent form and commit to attending the scheduled treatment dates. Participants receive an appointment card to attend sessions. An evaluator is responsible for notifying and monitoring the participants on a weekly basis (via telephone contact, WeChat, and/or email) and accompanying them during the research.
To ensure data quality control, the data manager conducts regular and timely data monitoring. When adding a new patient to the database, their identifying data is recorded on a printed form, which is not stored on the server. On this form, the participant's name is represented by a combination of four English letters (the initials of their Chinese name pronunciation). This form is securely stored in a locked space, accessible only to the principal investigator, and may be utilized to reveal personal data if the need arises for unblinding purposes. Access to the final dataset is restricted solely to the principal investigator and the statistician, ensuring confidentiality and maintaining the integrity of the data. The data management team will maintain ongoing communication with the investigators regarding the progress of the trial, data consistency, instances of missing data, and any violations of time windows. If needed, queries for missing data and requests for clarification of inconsistencies or discrepancies will be issued.
Statistics analysis
A comprehensive analysis is performed to delineate the demographic and clinical characteristics of the patient population. The normality of the variables is assessed using the Shapiro-Wilk test. The evaluated variables are depicted in tabular form, displaying both absolute and relative frequency distributions. Associations are examined utilizing either Pearson’s Chi-square test or Fisher’s exact test, as warranted. The statistical significance of mean differences among quantitative variables is assessed through the paired and unpaired t-Student tests. To assess variations across different time points within a group, the analysis of variance (ANOVA) with repeated measures is employed.
Continuous data are presented as mean ± standard deviation (SD), while categorical data are represented as counts (percentages). All analyses follow a two-tailed approach, with a significance level of 0.05. The statistical software package SPSS 17 (IBM Corporation, Armonk, NY) is employed for conducting data analysis, in accordance with established procedures.
In instances of data discontinuity, missing data will be handled in accordance with the 'intention-to-treat' principle for conducting inferential statistical analysis