Blepharoptosis After Repeated Intravitreal Anti-VEGF Injections: A Prospective Study

NCT07821450 | Not Yet Recruiting

• 1 other identifier: BLFRPTS-2026-01
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Age-Related Macular Degeneration; Blepharoptosis; Diabetic Macular Edema

Keywords

intravitreal injection; anti-VEGF; eyelid speculum; blepharostat; margin reflex distance; aponeurotic ptosis

Outcome Measures

Primary Outcomes (1)

• Between-eye difference in the change in margin reflex distance-1 (MRD-1) from baseline to month 12

  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.

  Baseline and 12 months

Secondary Outcomes (6)

• 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

Study Arms (1)

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.

Other: Repeated intravitreal anti-VEGF injection with eyelid speculum

Interventions

Repeated intravitreal anti-VEGF injection with eyelid speculum OTHER

Intravitreal anti-VEGF injection (ranibizumab, aflibercept or bevacizumab) given in the study eye on clinical indication under sterile conditions, topical anesthesia and with an eyelid speculum. Agent, interval and number of injections are determined by the treating retina specialist, not by the study.

Patients starting unilateral intravitreal anti-VEGF therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adults aged 18 years or older with a retinal disease (neovascular age-related macular degeneration, diabetic macular edema or retinal vein occlusion) scheduled to begin intravitreal anti-VEGF therapy in one eye only, with no history of intravitreal injection in either eye, recruited consecutively at a single tertiary ophthalmology clinic in Istanbul, Turkey.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Abdulkadir Küçük: lead

Study Sites (1)

University of Health Sciences, Fatih Sultan Mehmet Training and Research Hospital

Istanbul, Turkey (Türkiye)

Location

Related Publications (2)

• Bermudez-Castellanos I, Cruz Velasco A, Garcia DM, de la Hoz Montanana MR, Bengoa Gonzalez A, Sanchez Tocino H, Castro-Portillo E, Galindo-Ferreiro A. Blepharoptosis After Intravitreal Anti-VEGF Injections: A Prospective Study. Ophthalmic Plast Reconstr Surg. 2026 May-Jun 01;42(3):305-309. doi: 10.1097/IOP.0000000000003085. Epub 2025 Sep 29.

  PMID: 41022034 BACKGROUND

• Berco E, Ostrovsky M, Esomchukwu O, Zaks O, Schlesinger M, Molina EJC, Ben-Zaken SG, Shoham-Hazon N. Risk of ptosis following eyelid speculum assisted intravitreal anti-VEGF injections. Graefes Arch Clin Exp Ophthalmol. 2025 Jun;263(6):1711-1717. doi: 10.1007/s00417-025-06763-3. Epub 2025 Feb 13.

  PMID: 39945841 BACKGROUND

MeSH Terms

Conditions

Blepharoptosis; Macular Degeneration

Condition Hierarchy (Ancestors)

Eyelid Diseases; Eye Diseases; Retinal Degeneration; Retinal Diseases

Central Study Contacts

Abdulkadir Küçük, MD

CONTACT

+90 538 572 5722; akkucuk42@gmail.com

Fatih Çoban, MD

CONTACT

+90 5392346206

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 10, 2026
• First Posted: September 15, 2026
• Study Start: September 25, 2026
• Primary Completion (Estimated): December 25, 2027
• Study Completion (Estimated): January 5, 2028
• Last Updated: September 15, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)