title: Prevention of retinal detachment in Stickler syndrome: the Cambridge prophylactic cryotherapy protocol.
abstract: OBJECTIVE
  The Stickler syndromes are the most common causes of inherited and childhood retinal detachment; however, no consensus exists regarding the effectiveness of prophylactic intervention. We evaluate the long-term safety and efficacy of the Cambridge prophylactic cryotherapy protocol, a standardized retinal prophylactic treatment developed to prevent retinal detachment arising from giant retinal tears in type 1 Stickler syndrome.
  
  
  METHODS
  Retrospective comparative case series.
  
  
  METHODS
  Four hundred eighty seven patients with type 1 Stickler syndrome.
  
  
  METHODS
  Time to retinal detachment was compared between patients who received bilateral prophylaxis and untreated controls, with and without individual patient matching. Patients receiving unilateral prophylaxis (after fellow eye retinal detachment) were similarly compared with an appropriate control subgroup. Individual patient matching ensured equal age and follow-up between groups and that an appropriate control (who had not suffered a retinal detachment before the age at which their individually matched treatment patient underwent prophylactic treatment) was selected. Matching was blinded to outcome events. Individual patient matching protocols purposely weighted bias against the effectiveness of treatment. All treatment side effects are reported.
  
  
  METHODS
  Time to retinal detachment and side effects occurring after prophylactic treatment.
  
  
  RESULTS
  The bilateral control group (n = 194) had a 7.4-fold increased risk of retinal detachment compared to the bilateral prophylaxis group (n = 229) (hazard ratio [HR], 7.40; 95% confidence interval [CI], 4.53-12.08; P<0.001); the matched bilateral control group (n = 165) had a 5.0-fold increased risk compared to the matched bilateral prophylaxis group (n = 165) (HR, 4.97; 95% CI, 2.82-8.78; P<0.001). The unilateral control group (n = 104) had a 10.3-fold increased risk of retinal detachment compared to the unilateral prophylaxis group (n = 64) (HR, 10.29; 95% CI, 4.96-21.36; P<0.001); the matched unilateral control group (n = 39) had a 8.4-fold increased risk compared to the matched unilateral prophylaxis group (n = 39) (HR, 8.36; 95% CI, 3.24-21.57; P<0.001). No significant long-term side effects occurred.
  
  
  CONCLUSIONS
  In the largest global cohort of type 1 Stickler syndrome patients published, all analyses indicate that the Cambridge prophylactic cryotherapy protocol is safe and markedly reduces the risk of retinal detachment.
authors.affiliation: Vitreoretinal Service, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom.
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Fincham
authors.affiliation: Centre for Applied Medical Statistics (CAMS), University of Cambridge, Cambridge, United Kingdom.
authors.forename: Laura
authors.initials: L
authors.lastname: Pasea
authors.affiliation: School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, United Kingdom.
authors.forename: Christopher
authors.initials: C
authors.lastname: Carroll
authors.affiliation: Vitreoretinal Service, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom; Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Annie M
authors.initials: AM
authors.lastname: McNinch
authors.affiliation: Vitreoretinal Service, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom.
authors.forename: Arabella V
authors.initials: AV
authors.lastname: Poulson
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge, United Kingdom; Regional Molecular Genetics Laboratory, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom.
authors.forename: Allan J
authors.initials: AJ
authors.lastname: Richards
authors.affiliation: Vitreoretinal Service, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom.
authors.forename: John D
authors.initials: JD
authors.lastname: Scott
authors.affiliation: Vitreoretinal Service, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom; Department of Pathology, University of Cambridge, Cambridge, United Kingdom. Electronic address: mps34@cam.ac.uk.
authors.forename: Martin P
authors.initials: MP
authors.lastname: Snead
mesh_terms: D000293:Adolescent; D000328:Adult; D001168:Arthritis / Q000150:complications* / Q000175:diagnosis / Q000235:genetics; D002985:Clinical Protocols; D024043:Collagen Type II / Q000235:genetics; D003240:Connective Tissue Diseases / Q000150:complications* / Q000175:diagnosis / Q000235:genetics; D017679:Cryotherapy; D004252:DNA Mutational Analysis; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000150:complications* / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D008297:Male; D010375:Pedigree; D012163:Retinal Detachment / Q000150:complications / Q000175:diagnosis / Q000209:etiology / Q000235:genetics / Q000517:prevention & control*; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D055815:Young Adult
chemical_list: C499177:COL2A1 protein, human; D024043:Collagen Type II