Stickler syndrome (MIM#108300)

1. Prevention of retinal detachment in Stickler syndrome: the Cambridge Prophylactic Cryotherapy protocol (2848) Gregory S Fincham,1 Laura Pasea,2 Christopher Carroll,3Annie M McNinch,1,4Arabella V Poulson,1 Allan J Richards,4,5 John D Scott,1 Martin P Snead.1,4 1Vitreoretinal Service, Cambridge University NHS Foundation Trust, Addenbrooke’s Hospital, 2Centre for Applied Medical Statistics, University of Cambridge, 3School of Health and Related Research, University of Sheffield, 4Department of Pathology, University of Cambridge, United Kingdom, 5Regional Molecular Genetics Laboratory, Cambridge University NHS Foundation Trust, Addenbrooke’s Hospital. • Stickler syndrome (MIM#108300) • Progressive arthro-ophthalmopathy is the leading cause of childhood and inherited retinal detachment (RD). • Patients present with features illustrated in figures 1 to 6. • Type 1 Stickler syndrome patients carry the greatest risk of RD following giant retinal breaks at the ora serrata. 28 year old male 5. Pathognomonic type 1 vitreous phenotype 4. 3. Megaglobus and congenital myopia 6. Oral giant retinal tear and detachment Facial dysmorphia and hearing loss Midline palatal clefting 2. Spondyloepiphyseal dysplasia 1. Hypothesis Prophylactic cryotherapy to the ora serrata, where giant retinal breaks are predicted to occur, would reduce the rate of RD in type 1 Stickler syndrome. • Methods • Patients were divided into four groups for comparison before and after individual patient matching protocols: • Bilateral prophylaxis – cryoprophylaxis to both eyes (n=194) • Bilateral control – no previous cryoprophylaxis (n=229) • Unilateral prophylaxis – unilateral cryoprophylaxis following fellow eye RD (n=104) • Unilateral control – no unilateral cryoprophylaxis following fellow eye RD; subgroup of bilateral control (n=64) Figure 11. Kaplan-Meier plot of unmatched unilateral control versus prophylaxis group Figure 7. Prevalence of retinal detachment in control versus prophylaxis groups Figure 9. Kaplan-Meier plot of unmatched bilateral control versus prophylaxis group • Results • The prevalence of RD was significantly reduced in all groups receiving prophylaxis (see fig. 7) • Sex-adjusted hazard ratios were significantly higher in all groups who did not receive prophylaxis (see fig. 8) • Kaplan-Meier survival analysis demonstrated significant benefit to all groups receiving prophylaxis (see figs. 9 – 12). • Cryoprophylaxis given according to the Cambridge Prophylactic Cryotherapy protocol caused no long-term side effects. Conclusion In the largest global cohort of type 1 Stickler syndrome patients published to date, all analyses indicate that the Cambridge Prophylactic Cryotherapy protocol is safe and markedly reduces the rate of retinal detachment. Figure 10. Kaplan-Meier plot of matched bilateral control versus prophylaxis group Figure 8. Hazard ratios: effect without prophylaxis and 95% confidence intervals (*sex-adjusted) Figure 12. Kaplan-Meier plot of matched unilateral control versus prophylaxis group Correspondence: mps34@cam.ac.uk