Deterioration of Avellino corneal dystrophy in a Chinese family after LASIK

Abstract

AIM: To reveal the importance of TGFBI gene screening for candidates with a family history of corneal disease or granular opacities in corneal stroma before refractive surgery. METHODS: A 37-year-old male (proband) underwent bilateral laser-assisted in situ keratomileusis (LASIK) in 2002, with right vision decreased significantly in 2006. The proband and other 32 members of the family underwent a detailed ophthalmic examination, including vision acuity, intraocular pressure, slit-lamp photograph, fundus examination, optical coherence tomography (OCT) of cornea, and in vivo confocal microscope (IVCM) and peripheral blood was used for genomic DNA extraction. Seventeen TGFBI gene exons were analyzed via polymerase chain reaction amplification and direct sequencing. RESULTS: Slit-lamp, IVCM, and OCT images showed that a large amount of dense and confluent granular opaque were seen at the interfaces of the flap and remnant stromal bed in right and light degree in left eye. Sanger sequencing showed that there was a 371G>A mutation (CGC>CAC) in exon 4, which indicated that he harbored a heterozygote R124H mutation, identifying the diagnosis of Avellino corneal dystrophy (ACD). Among the other 32 family members, 6 of them harbored the identical mutation to that in the proband. CONCLUSION: ACD will worsen and recur after LASIK. Preoperative gene-screening for TGFBI mutations is important in diagnosing ACD.

Novel Manifestation of Corneal Dystrophy After Keratorefractive Surgery

“…However, the deposits observed in our patients exhibited distinct patterns and were located exclusively in the Bowman layer, in contrast to those in previous reports, in which the deposits were mainly located at the interface. 7,9,13 The deposits observed at the Bowman layer in Reis-Bucklers or Thiel-Behnke dystrophies bear resemblance to the OCT images shown in our study. However, distinct patterns were discerned in the slit-lamp images of our subjects.…”

“…The precise etiology underlying the selective deposition of these deposits in the Bowman layer remains incompletely understood, although some researchers suggest that differences in the proteoglycan content or the unique ultrastructural properties of the Bowman layer may play a role. 14 Although the exacerbation of corneal dystrophy after refractive surgery is mostly observed in GCD2 cases associated with TGFBI gene mutations as reported in previous studies, 7,9,[15][16][17] only one of our patients (case 3) exhibited a missense mutation on TGFBI: c.1949C.T (p. Ala650Val), which has never been linked to GCD2. One of our patients (case 2) presented with a missense mutation in SLC4A11, which is expressed in the corneal endothelium and is correlated with congenital hereditary endothelial dystrophy.…”

“…The literature includes several reports of exacerbated granular corneal dystrophy type 2 (GCD2) after laser-assisted in situ keratomileusis (LASIK), laser epithelial keratomileusis, radial keratotomy (RK), photorefractive keratectomy, and small-incision lenticule extraction (SMILE). [1][2][3][4][5][6][7][8][9] GCD2 is an autosomal dominant disorder linked to a TGFBI mutation that leads to corneal stromal hyaline and amyloid deposition. 6 The pathogenic mechanism underlying this unwanted side effect is the overproduction of TGF-b-induced proteins activated by corneal surface trauma during surgery, which results in corneal amyloid deposition within the corneas of patients with TGFBI mutations.…”

Association of a TGFBI Mutation with Congenital Glaucoma in GAPO Syndrome

“…A string analysis also showed that both TGFBI and LTBP2 (associated with congenital glaucoma) co-express, along with a possible interaction with MYOC and CYP1B1. There is also a report of glaucoma observed in a patient with TGFBI , R124H mutation, though the phenotypic details of this patient are not known (20). We also found 2 patients of ours with early onset open angle glaucoma with TGFBI mutations in a separate cohort.…”

Association of TGFBI variants with Congenital and Juvenile onset open angle glaucoma.

“…A string analysis also showed that TGFBI and LTBP2 (associated with congenital glaucoma) co-express, possibly interacting with MYOC and CYP1B1 . There is also a report of glaucoma observed in a patient withTGFBI, R124H mutation, though the phenotypic details of this patient are not known (Jiang & Zhang 2021).These observations suggest an important role of TGFBI in glaucoma pathogenesis, in conjunction with other genes.…”