Hereditary arthro-ophthalmopathy, more commonly referred to as Stickler syndrome, is a connective tissue disorder characterized by orofacial, musculoskeletal, auditory, and ocular abnormalities.1 Four distinct subgroups of this disorder have been described, each corresponding to a different mutation in genes encoding various collagen polypeptides.2 Ocular manifestations are most frequently seen in type 1 and type 2 Stickler syndrome, both of which are inherited in an autosomal dominant fashion.3
Defects in collagen result in strong vitreoretinal adhesions predisposing patients to retinal tears and detachments.4 The risk of rhegmatogenous retinal detachment (RD) has been cited to be as high as 70% in type 1 Stickler syndrome5 and between 40% to 50% in type 2 Stickler syndrome.6 In addition to the vitreoretinal abnormalities, the majority of patients with Stickler syndrome have a high degree of myopia.1 Congenital cataracts and glaucoma are also common.7,8
RD repair in Stickler syndrome presents a unique challenge to the vitreoretinal surgeon because of the propensity for giant retinal tears and proliferative vitreoretinopathy (PVR).2 Recent case series of RD repair in the Stickler population have shown rates of redetachment to be much higher than in typical RDs.9–12 This study aims to describe the anatomic and visual outcomes of RD repair in this condition.
Patients and Methods
This study was approved by the institutional review board of the Zucker School of Medicine at Hofstra/Northwell Health System and adhered to the tenets of the Declaration of Helsinki. This is a single-center, retrospective, interventional case series of 29 eyes of 22 patients with Stickler syndrome requiring RD repair between 1999 and 2017 at the Long Island Vitreoretinal consultants. The diagnosis of Stickler syndrome was based on exam and confirmed either by genetic studies or family history. Patients were required to have a minimum presenting visual acuity (VA) of light perception and follow-up of at least 12 months.
Preoperative age, gender, laterality of eye, VA, and type of retinal break were collected. The ocular lens status — whether phakic, pseudophakic, or aphakic — was also recorded. The type of retinal break was recorded into three categories: single tear, multiple retinal tears, and GRT. Eyes underwent either a scleral buckle (SB) only, pars plana vitrectomy (PPV) only, or a combined SB/PPV. The tamponading agent, whether gas or silicone oil, was documented for initial and subsequent surgeries.
Descriptive statistics were reported for each independent variable for each eye by type of surgery received. Means and standard deviations or medians and interquartile ranges (IQRs) were calculated for continuous variables, as applicable. Independent variables included number of patients receiving surgery for one or both eyes, type of initial surgery (PPV, SB, SB/PPV), age at the time of initial surgery, sex, laterality, logarithm of the minimum angle of resolution scores (logMAR) at presentation, PVR development at any point (Yes/No), type of break before surgery, length of follow-up in months and days, the number of surgeries, logMAR scores at the 1-year and last follow-up visit, phakic status, whether or not silicone oil was used at any time during course of treatment prior to last follow-up (Yes/No), and whether or not silicone oil was still present at 1 year and/or the last visit.
Outcome variables included attachment status at 1 year and at last follow-up visit, time to redetachment following the first surgery, and change in vision from pre-surgery to 1 year and to last follow-up. Marginal proportional hazards, linear mixed models and generalized linear mixed models were used, as appropriate.
The outcome, changes in vision from pre-surgery to 1 year and to last follow-up, was calculated by subtracting the pre-op logMAR from the logMAR at 1 year or last follow-up as appropriate. A decrease in logMAR scores (measured as a negative change in logMAR) indicates improved vision. A paired t-test was used to compare preoperative and postoperative visual acuities at 1 year and last follow-up. Tests for association were performed with each of the independent variables: preoperative logMAR, length of follow-up (days), laterality, number of surgeries, PVR at any point (Yes/No), silicone oil used (Yes/No), break type, and type of surgery. Univariate analysis was performed on the complete dataset, which comprised 29 eyes from 22 patients for each of the independent variables with the exclusion of type of surgery. For the analyses that included analysis with initial surgery group, only the 27 eyes from 21 patients whose initial surgery was SB or SB/PPV were included, as there were too few patients in the PPV group to be able to keep them in the analysis. Multivariable analyses were not performed due to sample size limitations. A result was considered significant if the P value was less than .05. All analyses were conducted using SAS version 9.4 (SAS Institute Inc., Cary, NC).
Twenty-nine eyes from 22 patients with Stickler syndrome underwent RD repair. The median number of months to last follow-up visit from first surgery was 54 (mean: 68 months, range: 12 to 200 months). Of the 22 patients, seven (32%) had surgery on both eyes. Among the 29 eyes, the initial surgery performed was PPV in two eyes (7%), SB in eight eyes (28%), and SB/PPV in 19 eyes (66%); median patient age at time of first surgery was 13 years old (IQR: 10 to 15 years). Nine of the patients (41%) were female. Fifteen of the eyes (52%) were right eyes and 14 (48%) were left eyes. Overall, 10 of the eyes (35%) treated had PVR at any point. Of the 29 eyes, the types of break observed were single breaks in six eyes (21%), multiple breaks in 12 eyes (41%), and GRTs in 11 eyes (38%). See Table 1 for a summary of patient demographics.
At 1-year follow-up, 29 of 29 eyes (100%) were attached. At last follow-up, 28 of 29 eyes (97%) were still attached and one (3%) was detached. Overall, 13 eyes (45%) had redetachments after the initial repair. The median number of surgeries per eye was two (mean: 2.3, range: 1 to 9). Silicone oil was used at any point during treatment in 12 eyes (41%). Three of these 12 eyes with silicone oil still had oil present at 1 year, and three had oil present at last follow-up. No significant association was observed between redetachment and type of break, or type of initial surgery.
Redetachment after first surgery was significantly associated with PVR at any time point (P < .01). The hazard ratio of redetachment after first surgery for eyes with PVR compared with eyes without PVR was 7.19 (95% confidence interval, 1.99–25.94). That is, eyes with PVR had a redetachment likelihood of approximately seven times greater than eyes without PVR.
The mean Snellen VAs at initial presentation, 1 year, and last follow-up visit were 20/289, 20/118 (P = .012), and 20/103 (P = .022), respectively. The number of eyes with 20/200 or better VA increased from 18 (62%) at initial presentation to 22 (76%) at 1 year, and 23 (79%) at the last follow-up. Those with 20/70 or better vision increased from 12 (41%) at initial presentation to 21 (72%) at 1 year, and 22 (76%) at the last follow-up.
For the univariate analyses with change in log-MAR vision as a continuous outcome (postoperative vision less the pre-op vision), a significant association was observed with preoperative logMAR vision (P < .01), with a −0.52 change in logMAR vision seen for each one-point increase in preoperative logMAR vision, where a negative change indicates an improvement in vision. No significant association was observed with number of surgeries, PVR development, silicone oil use, or type of retinal break. These associations were the same, regardless of whether the type of initial surgery was included in the model. See Table 2 for a summary of anatomic and visual outcomes.
Anatomic and Visual Outcomes of Retinal Detachment Repair in Stickler Syndrome
Stickler syndrome is a connective tissue disorder associated with a high risk of rhegmatogenous RD. Challenges unique to this disorder include the young age at which RDs tend to occur, the high prevalence of multiple tears or GRTs, and the high rates of PVR development. The level of difficulty in repairing RDs in this population is reflected by the low primary success rates reported in the literature. Studies have reported success rates after one surgery ranging from 19% to 78%,9–12 which is lower than the primary success rates seen in typical rhegmatogenous RDs.13 Final reattachment rates in Stickler syndrome after multiple attempts, however, are high ranging from 93% to 100%.10–12
In this series of 29 eyes, RD was achieved successfully in 28 of 29 eyes (97%), with a median of two surgeries per eye, including silicone oil removal surgeries. Fifty-five percent of eyes were attached successfully after the initial surgery. Our anatomic success rates, therefore, are consistent with those previously described in the literature. One distinction to be made about this series, however, is the relatively low percentage of eyes with silicone oil present at 1 year and at last follow-up. By the strictest criteria, absolute anatomical success can be defined as retinal reattachment without silicone oil tamponade remaining in the eye at the specified endpoint. Using this definition, 90% of the eyes met this definition of success irrespective of interim treatments in this study at 1-year follow-up. In comparison, the absolute success rates in the two previously published studies that included silicone oil usage in their data were 63% and 73%.10,11 Our study, therefore, suggests that true anatomic success can be achieved in the majority of eyes even after silicone oil tamponade removal. Long-term tamponade has many associated potential complications, including corneal opacities, band keratopathy, glaucoma, cataract, and silicone oil emulsification.
Redetachments occurred in 13 eyes (45%) after the initial repair. The mean interval between initial surgery and the first redetachment was 6.7 months, consistent with the intervals reported in prior studies, which ranged from 2.6 to 9.2 months.10–12 Excluding the one redetachment that occurred 4.7 years after the initial surgery (this was the one patient who had anatomical failure to ultimately stay reattached in our study), the mean interval between initial repair to first redetachment in our study was 47 days. The majority of redetachments (10 of 13 redetached eyes) occurred within 45 days of the initial surgery. This highlights the importance of close follow-up in the early postoperative period. Most detachments were caused by complications secondary to PVR, whereas others were caused by new breaks. In the univariable analyses, the only factor associated with an increased hazard of redetachment was the presence of PVR, as expected. Neither the type of tear nor the initial type of surgery had any statistically significant association with the risk of redetachment. However, we feel that there is selection bias with surgery type initially performed with worse cases receiving vitrectomy and SB initially, as one might expect.
Many patients experienced an improvement in vision postoperatively. The mean Snellen VAs at initial presentation, 1 year, and last follow-up were 20/289, 20/118 (P = .012), and 20/103 (P = .022), respectively. Due to the small sample size, few predictive factors of improved postoperative vision were identified. Notably, neither the type of tear, nor the initial surgery type was significantly associated with any particular visual outcome. On univariable analysis, however, decreased preoperative vision was associated with a greater improvement in vision at last follow-up. This is likely due to the healing effect after repairing macula-off detachments.
Lensectomies were required in six eyes, all of which were aphakic at last follow-up. All eyes in the lensectomy group underwent combined scleral buckling with vitrectomy at the initial surgery, though the lensectomy was not necessarily performed at the initial surgery. Silicone oil was also used in all six of these lensectomy eyes. At last follow-up, all of these eyes were attached, and VAs ranged from 20/70 to hand motion in these six eyes. However, two eyes still had silicone oil present at last follow-up.
A consensus regarding the best surgical approach to RD repair in the Stickler population has yet to be reached. A prior study found PPV to be more effective in achieving anatomic success compared to primary scleral buckling,10 whereas another study recommended combined scleral buckling and vitrectomy with silicone oil tamponade as the treatment of choice.12 In our cohort, no statistically significant differences were noted between primary SB, primary PPV, and combined SB/PPV.
Though the usual techniques have been reported for repair of these detachments, due to their high rate of PVR most are best treated with a combination of SB and vitrectomy at the initial surgery. If multiple tears are involved (or there is a GRT), then silicone oil is often helpful as part of the initial surgery. A lensectomy is not necessarily usually indicated. Additionally, if silicone oil is used in these patients, it can often be removed 2 to 3 months after the initial surgery (to help minimize cataract formation), unless PVR complicates the course. Additionally, intensive postoperative steroid treatment by mouth and topically helps minimize fibrin formation in these patients. There are cases where a SB alone is sufficient for treating a single retinal tear RD in these patients, but this situation is much less common.
With regard to prevention of RD in Stickler Syndrome the Cambridge Prophylactic Cryotherapy Protocol Study showed that this technique is safe and markedly reduced the risk of detachment in Type I Stickler patients.14 They showed approximately an eight-fold reduction in the risk of RD in the prophylactically treated groups (P < .001) of Type I patients with no significant long-term side effects from treatment. In the U.S. presently, most people are not treating with cryotherapy using this technique but are using laser in the same prescribed pattern taking care to treat the horizontal meridians less heavily with the laser to protect the long ciliary arteries and nerves. Some may use cryotherapy to treat the horizontal meridians, or if there is a significant cortical cataract wedge interfering with placement of the laser in the treatment target area. In patients with a previous GRT in one eye, there is evidence that prophylactic scleral buckling can also be helpful in the fellow eye to help prevent a GRT.15 We typically use a 220 style tire with a 240 style band (for 360°) in these cases, as well as in most of our Stickler RD repairs since the eyes are so large and the posterior vitreous base insertion is often more posterior than usual. We believe this approach has led to good outcomes in our cohort.
One limitation of this case series was the retrospective nature of the study, which relied heavily on the accuracy of the original documentation. Another limitation of this study was the small sample size, which limited the ability to build multivariable models, and therefore to properly account for confounding. In particular, we were unable to control for the type of surgery received, which may be confounded by the severity of the initial condition or other clinical factors.
Overall, anatomic success can be achieved in the majority of RDs associated with Stickler Syndrome. However, redetachments are common and multiple surgeries are often required to achieve long-term anatomic success. Reasonable visual recovery is also possible in many eyes. The authors of this study feel that combined scleral buckling with vitrectomy and silicone oil placement is often indicated for successful reattachment given the propensity for PVR in this population.
- Stickler GB, Hughes W, Houchin P. Clinical features of hereditary progressive arthro-ophthalmopathy (Stickler syndrome): a survey. Genet Med. 2001;3(3):192–196. doi:10.1097/00125817-200105000-00008 [CrossRef] PMID:11388760
- Snead MP, McNinch AM, Poulson AV, et al. Stickler syndrome, ocular-only variants and a key diagnostic role for the ophthalmologist. Eye (Lond). 2011;25(11):1389–1400. doi:10.1038/eye.2011.201 [CrossRef] PMID:21921955
- Snead MP, Yates JR. Clinical and Molecular genetics of Stickler syndrome. J Med Genet. 1999;36(5):353–359. PMID:10353778
- Parma ES, Körkkö J, Hagler WS, Ala-Kokko L. Radial perivascular retinal degeneration: a key to the clinical diagnosis of an ocular variant of Stickler syndrome with minimal or no systemic manifestations. Am J Ophthalmol. 2002;134(5):728–734. doi:10.1016/S0002-9394(02)01646-X [CrossRef] PMID:12429250
- Ang A, Poulson AV, Goodburn SF, Richards AJ, Scott JD, Snead MP. Retinal detachment and prophylaxis in type 1 Stickler syndrome. Ophthalmology. 2008;115(1):164–168. doi:10.1016/j.ophtha.2007.03.059 [CrossRef] PMID:17675240
- Poulson AV, Hooymans JM, Richards AJ, et al. Clinical features of type 2 Stickler syndrome. J Med Genet. 2004;41(8):e107 doi:10.1136/jmg.2004.018382 [CrossRef] PMID:15286167
- Seery CM, Pruett RC, Liberfarb RM, Cohen BZ. Distinctive cataract in the Stickler syndrome. Am J Ophthalmol. 1990;110(2):143–148. doi:10.1016/S0002-9394(14)76982-X [CrossRef] PMID:2378378
- Nielsen CE. Stickler's syndrome. Acta Ophthalmol (Copenh). 1981;59(2):286–295. doi:10.1111/j.1755-3768.1981.tb02991.x [CrossRef] PMID:7257747
- Billington BM, Leaver PK, McLeod D. Management of retinal detachment in the Wagner-Stickler syndrome. Trans Ophthalmol Soc U K. 1985;104(Pt 8):875–879. PMID:3868881
- Abeysiri P, Bunce C, da Cruz L. Outcomes of surgery for retinal detachment in patients with Stickler syndrome: a comparison of two sequential 20-year cohorts. Graefes Arch Clin Exp Ophthalmol. 2007;245(11):1633–1638. doi:10.1007/s00417-007-0609-2 [CrossRef] PMID:17579881
- Reddy DN, Yonekawa Y, Thomas BJ, Nudleman ED, Williams GA. Long-term surgical outcomes of retinal detachment in patients with Stickler syndrome. Clin Ophthalmol. 2016;10:1531–1534. doi:10.2147/OPTH.S111526 [CrossRef] PMID:27574392
- Alshahrani ST, Ghazi NG, Al-Rashaed S. Rhegmatogenous retinal detachments associated to Stickler syndrome in a tertiary eye care center in Saudi Arabia. Clin Ophthalmol. 2015;10:1–6. PMID:26730175
- Schaal S, Sherman MP, Barr CC, Kaplan HJ. Primary retinal detachment repair: comparison of 1-year outcomes of four surgical techniques. Retina. 2011;31(8):1500–1504. doi:10.1097/IAE.0b013e31820d3f55 [CrossRef] PMID:21606887
- Fincham GS, Pasea L, Carroll C, et al. Prevention of retinal detachment in Stickler syndrome: the Cambridge prophylactic cryotherapy protocol. Ophthalmology. 2014;121(8):1588–1597. doi:10.1016/j.ophtha.2014.02.022 [CrossRef] PMID:24793526
- Freeman HM. Fellow eyes of giant retinal breaks. Trans Am Ophthalmol Soc. 1978;76:343–382. PMID:754378
|Age (22 Patients), Years|
| Mean (median, range)||14 (13, 3–42)|
| Male||13 (59%)|
| Female||9 (41%)|
|Eye (29 Eyes; 22 Patients)|
| Right||15 (52%)|
| Left||14 (48%)|
|Duration of Follow-Up, Months|
| Mean (median, range, IQR)||68 (54, 12–200, 21–87)|
Anatomic and Visual Outcomes of Retinal Detachment Repair in Stickler Syndrome
|Initial Surgery Type||No. of Eyes||Single Tear, n (%)||Multiple Tears, n (%)||Giant Retinal Tear, n (%)||PVR at Any Point, n (%)||Success After Initial Surgery, n (%)||Anatomic Success at 1 Year, n (%)||Anatomic Success at Last Visit, n (%)||Average Change in logMAR at 1 Year||Average Change in logMAR at Last Visit|
|SB||8||1 (12)||7 (88)||0 (0)||1 (12)||5 (62)||8 (100)||8 (100)||−0.12||−0.41|
|PPV||2||1 (50)||1 (50)||0 (0)||1 (50)||1 (50)||2 (100)||2 (100)||−0.30||−0.86|
|SB/PPV||19||4 (21)||4 (21)||11 (58)||8 (42)||10 (53)||19 (100)||18 (95)||−0.51||−0.41|
|Overall||29||6 (21)||12 (41)||11 (38)||10 (35)||16 (55)||29 (100)||28 (97)||−0.38||−0.44|