Prospective Evaluation of Blepharoptosis Development in Patients Undergoing Repeated Intravitreal Anti-VEGF Injections
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Between-eye difference in the change in margin reflex distance-1 (MRD-1) from baseline to month 12
研究概览
简要总结
Intravitreal anti-VEGF injections are a mainstay of treatment for retinal diseases such as neovascular age-related macular degeneration, diabetic macular edema and retinal vein occlusion, and usually require repeated administration over years. During each injection an eyelid speculum holds the lids open and the upper eyelid is exposed to repeated mechanical stretch. Aponeurotic ptosis after intraocular surgery is well described, but evidence on blepharoptosis after repeated intravitreal injections is limited and conflicting.
This single-center prospective observational study enrolls 60 patients who are starting intravitreal anti-VEGF therapy in one eye only; the untreated fellow eye of each patient serves as an internal control. Upper eyelid position and function are assessed with margin reflex distance-1 (MRD-1), margin reflex distance-2 (MRD-2) and levator function at baseline and at months 1, 3, 6 and 12. The primary endpoint is the difference between the injected eye and the fellow eye in the change in MRD-1 from baseline to month 12.
详细描述
Design: prospective, single-center, longitudinal, non-interventional observational study conducted in the Department of Ophthalmology, University of Health Sciences, Fatih Sultan Mehmet Training and Research Hospital, Istanbul, Turkey.
No study-driven intervention is performed. The decision to treat, the anti-VEGF agent (ranibizumab, aflibercept or bevacizumab), the injection interval and the total number of injections are determined solely by the treating retina specialist on clinical grounds. Injections are given under routine sterile conditions, topical anesthesia and with an eyelid speculum, as in standard practice; the study therefore evaluates the combined exposure of injection plus speculum use and cannot isolate the speculum-specific mechanical effect.
The injected eye is the study eye and the non-injected fellow eye is the control eye; each participant serves as their own control. All participants are assessed at baseline and at months 1, 3, 6 and 12. At every visit, for both eyes, MRD-1, MRD-2 and levator function are measured by the same examiner where possible using a standard technique. MRD-1 is the distance in millimetres between the corneal light reflex and the upper eyelid margin in primary gaze; MRD-2 is the distance between the corneal light reflex and the lower eyelid margin; levator function is the upper eyelid excursion from downgaze to upgaze with frontalis action neutralised. The cumulative number of intravitreal injections, the agent used and the number of eyelid speculum uses are recorded at each visit. Clinically significant blepharoptosis is defined as an MRD-1 of 2 mm or less and/or a decrease of 2 mm or more from baseline, evaluated separately for each eye at every visit.
Sample size: based on a paired comparison of the change in MRD-1. Using the 0.60 mm (SD 0.61) MRD-1 reduction at 12 months reported by Bermudez-Castellanos et al., and assuming a conservatively clinically meaningful difference of 0.50 mm with a standard deviation of paired differences of 1.00 mm (dz = 0.50), a two-sided alpha of 0.05 and 90% power require a minimum of 44 evaluable participants; allowing for approximately 25% attrition over 12 months, the target enrollment is 60.
Statistical analysis
normality by the Shapiro-Wilk test; between-eye change compared by paired t-test or Wilcoxon signed-rank test; repeated measures across the five timepoints by repeated-measures ANOVA or the Friedman test; frequency of clinically significant blepharoptosis compared between eyes by the McNemar test; associations between the number of injections or speculum uses and the change in eyelid measurements by Pearson or Spearman correlation; a sensitivity analysis compares eyelid measurement change among anti-VEGF agents. Two-sided p < 0.05 is considered significant. Analyses are performed in SPSS.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 years or older
- •Planned initiation of intravitreal anti-VEGF injection in one eye only for a retinal disease
- •No prior intravitreal injection in either eye
- •Able to attend the scheduled follow-up visits and to cooperate for the duration of the study
- •Reliable MRD-1, MRD-2 and levator function measurement possible in both eyes (clear corneal light reflex, clearly visible eyelid margin, able to maintain primary gaze)
- •Signed informed consent
排除标准
- •Pre-existing blepharoptosis or significant eyelid malposition at the baseline examination
- •Previous ptosis surgery, blepharoplasty or other eyelid surgery that may affect upper eyelid anatomy
- •History of myasthenia gravis, oculomotor nerve palsy, Horner syndrome, facial nerve palsy or a similar neurologic or neuromuscular disorder
- •History of orbital trauma, orbital surgery or orbital disease
- •Advanced dermatochalasis, eyelid retraction, entropion, ectropion or marked facial asymmetry precluding reliable eyelid measurement
- •Need for intravitreal injection in both eyes during the study period
- •Ocular or periocular surgery during follow-up that may affect upper eyelid position
- •Inability to comply with follow-up visits or incomplete measurements
- •Withdrawal of consent
- •Inability to obtain reliable eyelid measurements due to severe blepharospasm, advanced corneal opacity, marked eyelid edema, or inability to maintain head or neck position or to cooperate
研究组 & 干预措施
Patients starting unilateral intravitreal anti-VEGF therapy
Adults with a retinal disease starting intravitreal anti-VEGF injections in one eye only. In each participant the injected eye is the study eye and the non-injected fellow eye is the internal control. Both eyes are assessed for MRD-1, MRD-2 and levator function at baseline and at months 1, 3, 6 and 12.
干预措施: Repeated intravitreal anti-VEGF injection with eyelid speculum (Other)
结局指标
主要结局
Between-eye difference in the change in margin reflex distance-1 (MRD-1) from baseline to month 12
时间窗: Baseline and 12 months
MRD-1 (mm) is the distance between the corneal light reflex and the upper eyelid margin in primary gaze. For each patient the change from baseline to month 12 in the injected (study) eye is compared with the corresponding change in the non-injected fellow (control) eye.
次要结局
- Between-eye difference in the change in margin reflex distance-2 (MRD-2) from baseline to month 12(Baseline and 12 months)
- Between-eye difference in the change in levator function from baseline to month 12(Baseline and 12 months)
- Longitudinal change in MRD-1, MRD-2 and levator function across visits(Baseline, 1, 3, 6 and 12 months)
- Incidence of clinically significant blepharoptosis(12 months)
- Association between cumulative intravitreal injection number and change in eyelid measurements(12 months)
- Change in eyelid measurements by anti-VEGF agent(12 months)
研究者
Abdulkadir Küçük
Principal Investigator
Fatih Sultan Mehmet Training and Research Hospital