Stickler Syndrome Type 1, Stickler Syndrome Type 2
Conditions
Keywords
prophylactic laser retinopexy, Ora Secunda Cerclage, laser, prophylactic, retinopexy, Stickler syndrome, retinal detachment, retinal tear, Stickler syndrome type 2, giant retinal tear, encircling laser prevention, Stickler syndrome type 1, GRT
Brief summary
The goal of this clinical trial is to prospectively document to what extent the OSC/SS prophylactic laser retinopexy procedure works to prevent retinal detachment in SS in children and adults. Researchers will compare the OSC/SS procedure in SS to the natural progression of SS to see to what extent the OSC/SS procedure works to prevent retinal detachment. Participants will: * Have the OSC/SS procedure in one or both eyes * Have eye tests * Have genetic testing for SS as needed * Visit the study center 9 times over 5 years for checkups and tests * Have data for the untreated fellow-eye collected and used as study data if available
Detailed description
Prophylactic treatment for RD has been well-documented to be safe and effective for specific predisposing conditions, but parameters are not standardized and are poorly documented in the literature for Stickler syndrome. There is significant, but only retrospective, evidence in the scientific literature that non-invasive, encircling (360 degree) laser prophylaxis (cerclage prophylaxis) reduces the rate of retinal detachment in patients with Stickler syndrome by approximately five-fold. In February 2025, the American Academy of Ophthalmology (AAO) endorsed 360-degree cerclage laser prophylaxis for Stickler syndrome based on retrospective evidence. A statistical review of pertinent articles concluded that prophylactic laser therapy was associated with a significantly lower risk of retinal detachment in patients with Stickler syndrome compared to no laser prophylaxis. This clinical trial is designed to offer OSC/SS as the optimal form of such prevention, and to prospectively document, in a standardized manner, the extent to which it prevents retinal detachment in patients with Stickler syndrome. This clinical trial aims to address the lack of standardized documentation in previous literature and studies by providing standardized treatment parameters and rigorously documenting the OSC/SS technique. By evaluating the safety and efficacy of OSC/SS in preventing RD in Stickler syndrome patients, this study seeks to establish a benchmark for future clinical practice and research. The primary objective is to demonstrate the efficacy of the OSC/SS procedure compared to the natural progression of SS to prevent RD for individuals with SS. This comparison will be made using historical control data provided by Cambridge University, which documents the rate of occurrence of RD in the absence of prior prophylactic treatment. Cambridge University maintains a large SS database, consisting of decades of clinical and research data on Stickler syndrome populations, providing the necessary control raw data for this study population. If the OSC/SS procedure proves to be adequately successful in the study, then it may become the gold standard treatment used to prevent RD in patients with SS and, with modifications, other populations at high risk for RD. Enrollment is competitive.
Interventions
PROCEDUREProphylactic (non-invasive) Laser Retinopexy
Prophylactic laser retinopexy to prevent RD in participants with SS using the indirect ophthalmoscopy (IDO) to place approximately 1500 to 2500 moderate intensity burns to produce encircling grid pattern, placed one burn width apart from 2 MM anterior to the ora serrata, extending to and between the vortex vein ampullae.
Sponsors
Helen Keller Eye Research Foundation
Five Lakes Clinical Research Consulting, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
1. No contraindications to laser retinopexy surgery per local site criteria. 2. Capable of giving signed informed consent, and assent (as appropriate) 3. Signature of research informed consent form from participant, or participant's legally authorized representative (LAR)/parent(s)/legal guardian 4. Male or female of any age 5. SS type 1 or type 2 confirmed by genetic testing
Exclusion criteria
1. Presence of media opacity (for example, dense cataract, corneal scar) or poor pupillary dilation that precludes adequate OSC/SS performance, laser treatment, or imaging. 2. Prior prophylactic laser treatment that cannot be supplemented to achieve a complete OSC/SS pattern or exceeds the designated OSC/SS pattern. 3. RD in the eye to be treated. 4. Significant intraocular hemorrhage in the eye to be treated. 5. Uncontrolled ocular conditions (e.g., glaucoma) that may be worsened by the procedure or preclude follow-up. 6. Any other ocular condition that precludes the ability to perform adequate laser treatment under scleral depression. 7. Any systemic medical contraindication where the risk of intervention outweighs the potential benefit. 8. Known pathogenic mutations in genes associated with other inherited retinal detachment syndromes, including but not limited to: FEVR-related genes: FZD4, LRP5, TSPAN12, NDPX-linked retinoschisis (RS1) Wagner Syndrome (VCAN). 9. Other syndromes associated with increased risk of retinal detachment (for example, Knobloch syndrome, Marfan syndrome, Pierson syndrome). 10. History of Coats disease. 11. History of Retinopathy of Prematurity (with or without laser treatment). 12. Prior laser photocoagulation in the study eye for any indication other than the following: retinal detachment prophylaxis for Stickler syndrome, treatment of lattice degeneration, or treatment of retinal tears. 13. Laser photocoagulation, for the indications permitted in
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with SS who Develop RD After Undergoing the OSC/SS Procedure as Assessed by One of the Following Photographic Fundus Mapping and IDO Examinations | From enrollment to post initial procedure at 5 years | Efficacy of the OSC/SS procedure in preventing RD in participants with type 1 (STL1) and type 2 (STL2) SS will be assessed annually by tracking the number of participants who develop RD after undergoing the OSC/SS procedure, using data from one of the following: photographic fundus mapping and IDO examinations. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Occurrences of Retinal Defects | From enrollment to post initial procedure at 5 years | Annually assess by tracking the number of occurrences of participants experiencing retinal defects including giant retinal tears after undergoing the OSC/SS procedure, using the number of unique retinal defect forms received for each participant. |
| Number of Participants Experiencing Retinal Defects | From enrollment to post initial procedure at 5 years | Annually assess by tracking the number of participants experiencing retinal defects after undergoing the OSC/SS procedure, using data from one of the following: photographic fundus mapping and IDO examinations. |
| Number of Surgeries to Repair Retinal Detachments or Retinal Defects | From enrollment to post initial procedure at 5 years | Annually assess by tracking the number of surgeries to repair retinal detachments or retinal defects in participants after undergoing the OSC/SS procedure, using the number of surgeries documented on the retinal defect forms received for each participant. |
| Measurement of Visual Acuity in Participants with SS Before and After the OSC/SS Procedure as Assessed by Using Standard of Care Methods | From enrollment to post initial procedure at 5 years | Impact of the OSC/SS procedure on visual acuity in participants with SS will be measured by standard of care methods including visual acuity charts and optical coherence tomography (OCT) imaging of the macula. |
| Number of Procedure Deviations by Treating Physicians as Assessed by Photographic Fundus Mapping | 3 to 6 months post OSC/SS procedure | Evaluate the compliance of treating physicians in correctly performing the OSC/SS procedure on participants with SS by tracking the number of procedure deviations including protocol specified grid coverage, burn spacing, and burn intensity by conducting a central review of photographic fundus mapping. |
| Size of Retinal Defects | From enrollment to post initial procedure at 5 years | Annually assess the size (measured in clock hours) of retinal defects including giant retinal tears (GRT) in participants experiencing retinal defects after undergoing the OSC/SS procedure, using IDO examinations compared to the natural course of SS. |
| Frequency of Adverse Events as Assessed by Recurring Eye Evaluations (photographic fundus mapping, OCT, intraocular pressure, pupil measurements, slit lamp biomicroscopy, motility assessments, and vision acuity testing) | From enrollment to post initial procedure at 5 years | Annual evaluation of the safety of the OSC/SS procedure will be assessed by reviewing adverse events collected from recurring visual history and eye evaluations (photographic fundus mapping, OCT, intraocular pressure, pupil measurements, slit lamp biomicroscopy, motility assessments, and vision acuity testing). |
Countries
United States
Contacts
CONTACTPeter J Belin, MD
CONTACTFive Lakes Clinical Research Consultants, LLC
STUDY_DIRECTORRobert E Morris, MD
Helen Keller Eye Research Foundation
PRINCIPAL_INVESTIGATORPeter J Belin, MD
Retina Consultants of Minnesota
Outcome results
None listed