Optical Coherence Tomography Imaging of the Vitreoretinal Interface in Type II

Abstract

Stickler syndrome was previously characterized post-enucleation by incarcerated vitreous within glial tissue of patients with retinal detachments.1 This study demonstrates similar vitreoretinal interfaces in vivo using OCT imaging of three siblings with Stickler Syndrome.

I. Case History

Patient A: 1. Demographics: 38 YOWM 2. Chief Complaint: None 3. Ocular, medical history: Type II Stickler Syndrome, diagnosed age 7 4. Medications: None 5. Other salient information: Mild 6. Family History a. Six Retinal detachments and two flap tears among first-degree relatives b. Twelve Retinal detachments among second-degree relatives c. Fourteen Retinal detachments among third-degree relatives

Patient B: 1. Demographics: 36 YOWM 2. Chief Complaint: None 3. Ocular, medical history: a. Type II Stickler Syndrome, diagnosed age 5 b. Flap tear OD, age 17, treated with retinopexy c. Flap tear OS, age 20, treated with retinopexy d. Vitreal tuft with photopsias OD, age 22, treated with retinopexy e. Central Serous Retinopathy OD, age 23, resolved 4. Medications: None 5. Other salient information: Mild myopia 6. Family History a. Six Retinal detachments among first-degree relatives b. Twelve Retinal detachments among second-degree relatives c. Fourteen Retinal detachments among third-degree relatives

Patient C: 1. Demographics: 34 YOWF 2. Chief Complaint: None 3. Ocular, medical history: a. Type II Stickler Syndrome, diagnosed age 3 b. Congenital OU 4. Medications: None 5. Other salient information: Mild myopia and moderate astigmatism 6. Family History a. Six Retinal detachments and two flap tears among first-degree relatives b. Twelve Retinal detachments among second-degree relatives c. Fourteen Retinal detachments among third-degree relatives

II. Pertinent Findings

Patient A: 1. Clinical: a. BCVA: 20/15 OD, OS b. Anterior segment: unremarkable c. TA: 18 OD, OS d. Posterior segment: Significant vitreal syneresis in excess to age-appropriate findings and vitreous beading e. OCT: Abnormal vitreal architecture; significant tubular collagen condensations at the vitreoretinal interface with approximation to the ILM, non-homogenous posterior hyaloid face OU 2. Physical: No systemic manifestations of Stickler Syndrome 3. Laboratory studies: None 4. Radiology studies: None

Patient B: 1. Clinical: a. BCVA: 20/20 OD, OS b. Anterior segment: unremarkable c. TA: 16 OD, OS d. Posterior segment: i. Significant vitreal syneresis in excess to age-appropriate findings and vitreous beading ii. Flap tear superior temporal OD, superior nasal OS, adequate barricade laser iii. Faint laser scars temporal OD iv. RPE disruption inferior nasal to fovea OD v. Lattice superior OD e. OCT: Abnormal vitreal architecture; significant tubular collagen condensations at the vitreoretinal interface with approximation to the ILM, non-homogenous posterior hyaloid face OD>OS 2. Physical: No systemic manifestations of Stickler Syndrome 3. Laboratory studies: None 4. Radiology studies: None

Patient C: 1. Clinical: a. BCVA: 20/20 OD, 20/25- OS b. Anterior segment: : Scattered punctate opacities in cortex OU, dense congenital superior temporal OS c. TA: 19 OD, 16 OS d. Posterior segment: i. Significant vitreal sheathing and vitreous beading ii. Lattice without holes superior and superior nasal OD, superior and inferior temporal OS e. OCT: Unremarkable OD, OS? 2. Physical: No systemic manifestations of Stickler Syndrome 3. Laboratory studies: None 4. Radiology studies: None

III. Differential Diagnosis

1. Differentials for Type II Stickler Syndrome:5 6 a. Type I, III, and IV Stickler Syndrome b. Knobloch Syndrome c. Wagner Syndrome d. Multiple Epiphyseal Dysplasia e. Metatropic Dysplasia f. Erosive Vitreoretinopathy g. h. Weissenbacker-Zweymuller Syndrome/OSMED i. j. Spondyloepiphyseal Dysplasia Congenita k. 2. Differentials for vitreal beading: None found in literature

IV. Diagnosis and Discussion

Stickler syndrome is arguably the most common autosomal dominant chondrodysplasia, characterized by ophthalmic abonormalities, early joint hypermobility and late osteoarthritis, sensorineural deafness, and variable orofacial features, including depressed nasal bridge, midline clefting, and micrognathia.6 Ophthalmic manifestations include paravascular lattice degeneration, mild to moderate myopia, congenital cataracts, retinal tears and detachments, and pathognomonic abnormalities in vitreous architecture.2 6

Type I Stickler syndrome, compromising 75% of all Stickler patients, occurs with in the COL2AI gene causing a variation in type II collagen leading to a “membranous” anomaly of the vitreous cavity, while patients with type II Sticklers develop mutations in COLIIAI, leading to type XI collagen abnormalities and a “beaded” vitreous phenotype.2 One study by ME MacRae et al., utilizing histological and electron microscopic examination of an enucleated of a patient with type I Stickler syndrome, discovered paramount abnormalities within the vitreoretinal interface, specifically adherence between vitreous collagen and retinal glial tissue in areas of detachment, in some cases forming a retrolental membrane of incarcerated collagen within glial strands.1 There are currently no studies in the literature that assess the presence or absence of collagen abnormalities within the posterior vitreous and vitreoretinal interface using OCT imaging of patients with type II Stickler syndrome.

V. Treatment, Management

Treatment for Stickler Syndrome is palliative, usually involving hearing assessment and management of sensorineural deafness, as well as thorough, lifelong ophthalmic care including corrective lenses for , cataract surgery, prophylactic retinopexy for retinal tears, and repair when indicated. Because Stickler Syndrome is the leading cause of rhegmatogenous retinal detachments in youth, patient education about symptoms of retinal detachment is crucial upon diagnosis.6

VI. Conclusion

This study demonstrates the ability of OCT imaging to elucidate abnormal vitreous architecture in Type II Stickler Syndrome. This method has not been previously explored in the literature. While statistically underpowered, there does not appear to be strong correlation between OCT findings and the prevalence of retinal defects.

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2. Poulson, A. V., Hooymans, J M M., Richards A. J. et al. (2004). Clinical features of type 2 Stickler syndrome. Journal of Medical Genetics, 41(8). doi:10.1136/jmg.2004.018382.

3. Richards, A. J., Mcninch, A., Martin, H. et al. (2010). Stickler syndrome and the vitreous phenotype: Mutations in COL2A1 and COL11A1. Human Hum. Mutat., 31(6). doi:10.1002/humu.21257.

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7. Wang, X., Xiaoyun, J., Xueshan, X. et al. (2016, June 23). Mutation survey and genotype- phenotype analysis of COL2A1 and COL11A1 genes in 16 Chinese patients with Stickler syndrome. Molecular Vision, 22, 697-704.