Genetically Predisposed to Capsular Bag Instability

Anchor-Assisted Capsular Bag IOL Implantation to Correct Subluxated Lenses in Children With Marfan Syndrome: Long-Term Follow-up

Yehezkeli V, Greenbaum E, Belkin A, Assia EI, Crystal-Shalit O, Ela-Dalman N¹

Industry support for this study: None

ABSTRACT SUMMARY 

This retrospective study reviewed the long-term visual and refractive outcomes and complications of scleral bag fixation in 10 consecutive eyes of eight pediatric patients (2–13 years old) with Marfan syndrome who underwent surgery for lens subluxation at a single center. A single AssiAnchor (Hanita Lenses) was implanted in each eye to anchor the capsular bag to the sclera. The device was inserted into the capsular bag after the capsulorhexis was fashioned and secured to the sclera with a polypropylene or PTFE suture. In all cases, an IOL was implanted in the capsular bag without complications and without the need for vitrectomy. Capsular tension rings were placed in 60% of eyes. Posterior capsulotomies were not performed intraoperatively due to concern about bag stability. 

An Nd:YAG laser capsulotomy was performed on 60% of eyes postoperatively. After a mean follow-up period of 5.08 years (2–9.25 years), patients’ corrected distance visual acuity improved from a mean of 20/80 to 20/30 (P < .01), with a mean absolute error from the refractive target of -0.37 ±0.60 D. Eight of the 10 IOLs remained stable without suture exposure. One patient experienced bilateral IOL subluxation 5 months after surgery, possibly due to eye rubbing, and underwent direct scleral fixation of both IOLs. Amblyopia (defined as a visual acuity worse than 20/30) was diagnosed in 60% of eyes; most cases were mild. One patient developed glaucoma.

DISCUSSION 

Patients with Marfan syndrome, a connective tissue disorder caused by mutations in the FBN1 gene, often develop lens subluxation. If these patients cannot obtain adequate visual function with spectacles, they may require early lensectomy. Given the lack of capsular support in these eyes, direct scleral or iris fixation of the IOL, anterior chamber implantation, or scleral suture fixation of modified capsular tension rings have been performed.  

All patients in this case series underwent IOL implantation in the bag using an AssiAnchor. Five years postoperatively, capsular stability and patients’ visual acuities were good, and no vitrectomy was required. A lower rate of IOL dislocation was reported in this study than has been reported in patients with Marfan syndrome who underwent scleral lens fixation.²

Limitations of this study¹ included the small number of patients and a follow-up period of several years. Progressive zonular loss could lead to IOL subluxation longer term, and the placement of multiple capsular anchors might be required to improve long-term stability. 

Genetic Variants in Genes Regulating Lens Capsule Structure and Stability in Dead Bag Syndrome: Part 1

Vasavada AR, Rajkumar S, Vasavada SA, Vasavada V, Dholu S, Meena V³

Industry support for this study: None

ABSTRACT SUMMARY 

This laboratory study investigated whether genetic variants affecting the lens capsule were associated with dead bag syndrome (DBS). Whole-exome sequencing was performed on blood samples collected from 30 patients with unilateral (n = 20) or bilateral (n = 10) DBS presenting with IOL dislocation, 29 age- and sex-matched controls who underwent uncomplicated cataract surgery, and eight age-matched controls without cataract. Rare genetic variants related to lens capsule structure and stability were assessed for association with DBS using the Optimal Unified Sequence Kernel Association test package, which may be used in case-control studies with small sample sizes to assess associations of rare variants with phenotypes.⁴ Logistic regression was used to assess the direction and strength of association. The Ensembl Variant Effect Predictor was used to predict the effect of identified genetic variants. 

The analysis found that three genes were associated with DBS: FBN2 (odds ratio [OR] = 4.9, P = .27, 95% CI = 0.56–42.72), LAMB1 (OR = 11.0, P = .005, 95% CI = 1.56–77.31), and LAMB2 (OR = 8.2, P = .91, 95% CI = 1.03–65.57). ITGB3 (OR = 1.4, P =.45, 95% CI = 0.01–260.92) and FN1 (OR = 40.9, P = .3, 95% CI = 1.53–1,094.27) were positively associated with DBS but were excluded from further analysis owing to large confidence intervals. 

Fifteen functionally harmful genetic variants were identified. Six variants in FBN2 negatively affected the protein structure of fibrillin 2. Three variants in LAMB1 negatively affected the laminin beta 1 chain, including the variant p.lle1547Thr (c.4640T>C), which was identified in five patients with DBS and no controls. Six variants in LAMB2 negatively affected the laminin beta 2 chain. All three proteins are known to be involved in lens capsule and/or zonular function.

DISCUSSION 

DBS can result in progressive postoperative thinning and spontaneous rupture of the posterior capsule, usually long after uneventful cataract surgery. The capsules of patients with DBS typically demonstrate a decrease in lens epithelial cells, but the condition was not previously known to be associated with genetic variants affecting lens capsule proteins. This study found that variants in three genes related to lens capsule proteins (laminins) and zonular function (fibrillin 2) were associated with DBS. Interestingly, 56.7% of patients with unilateral DBS and 70% of patients with bilateral DBS had a variant in genes related to the lens capsule, demonstrating for the first time a possible genetic basis for the condition.