Graft rejection after deep anterior lamellar keratoplasty in fellow eye in macular corneal dystrophy: a case report

Because of the low incidence of immunological rejection,deep anterior lamellar keratoplasty(DALK)is currently the preferred treatment for macular corneal dystrophy(MCD).However,there were few reports about whether the consistent results were obtained when performing DALK in both eyes for MCD,especially when the corneal grafts were taken from different donors.Also,there were few reports about whether the stromal graft rejection occurred typically in both eyes in MCD with DALK.This case may represent the first report of an unusual and misleading manifestation of stromal graft rejection after uneventful DALK with big bubble technique in the fellow eye in MCD.A 32-year-old healthy man with MCD underwent bilateral uneventful DALK with a big bubble technique in the left eye in January and the right eye in July,the corneal grafts were taken from different donors.There was an atypical allograft rejection that occurred in the right eye and none in the left eye;although a timely diagnosis of graft rejection revealed following aqueous determination,it could not be reversed and underwent PK finally.The purpose of this case report is to illustrate the identification of atypical allograft rejection after DALK in the fellow eye,the significance of aqueous detection in the diagnosis of graft rejection,the choosing of grafts,and the timing of bilateral corneal transplantation in patients with MCD.

The role of corneal endothelium in macular corneal dystrophy development and recurrence

Macular corneal dystrophy(MCD)is a progressive,bilateral stromal dystrophic disease that arises from mutations in carbohydrate sulfotransferase 6(CHST6).Corneal transplantation is the ultimate therapeutic solution for MCD patients.Unfortunately,postoperative recurrence remains a significant challenge.We conducted a retrospective review of a clinical cohort comprising 102 MCD patients with 124 eyes that underwent either penetrating keratoplasty(PKP)or deep anterior lamellar keratoplasty(DALK).Our results revealed that the recurrence rate was nearly three times higher in the DALK group(39.13%,9/23 eyes)compared with the PKP group(10.89%,11/101 eyes),suggesting that surgical replacement of the corneal endothelium for treating MCD is advisable to prevent postoperative recurrence.Our experimental data confirmed the robust m RNA and protein expression of CHST6 in human corneal endothelium and the rodent homolog CHST5 in mouse endothelium.Selective knockdown of wild-type Chst5 in mouse corneal endothelium(AC^(siChst5)),but not in the corneal stroma,induced experimental MCD with similar extracellular matrix synthesis impairments and corneal thinning as observed in MCD patients.Mice carrying Chst5 point mutation also recapitulated clinical phenotypes of MCD,along with corneal endothelial abnormalities.Intracameral injection of wild-type Chst5 rescued the corneal impairments in AC^(siChst5)mice and retarded the disease progression in Chst5 mutant mice.Overall,our study provides new mechanistic insights and therapeutic approaches for MCD treatment by highlighting the role of corneal endothelium in MCD development.

Novel mutations in the BEST1 gene cause distinct retinopathies in two Chinese families

AIM:To describe the clinical heterogeneity of patients with novel mutations in BEST1.METHODS:All the members in the two Chinese families underwent detailed clinical evaluations including best-corrected visual acuity,slit-lamp examination,applanation tonometry,and dilated fundus examination.Fundus autofluorescence,fundus fluorescein angiography,spectral-domain optical coherence tomography,electrooculography,and electroretinogram were also performed.Genomic DNA was extracted from venous blood for all the participants.The targeted next-generation sequencing of inherited retinal disease-associated genes was conducted to identify the causative mutation.RESULTS:A novel BEST1 missense mutation c.41T>C(p.Leu14Ser) was identified in Family 1.It was co-segregated with the phenotype of best vitelliform macular dystrophy(BVMD) and bioinformatics analysis confirmed it was harmful.Another novel BEST1 frameshift mutation c.345_(3)46insGGCAAGGACG(p.Glu119Glyfs*116) and a novel USH2A missense mutation c.12560G>A,p.Arg4187 His were identified in family 2 with retinitis pigmentosa(RP),which might interact and lead to the phenotype of RP.CONCLUSION:Two novel mutations in the BEST1 gene in two unrelated families with distinct phenotypes and BEST1 mutation accompanied with USH2A mutation would result in RP,which could be enormously helpful in understanding the pathogenesis of the inherited retinal disease caused by a BEST1 mutation.

Retinal imaging in inherited retinal diseases

Inherited retinal diseases(IRD)are a leading cause of blindness in the working age population.The advances in ocular genetics,retinal imaging and molecular biology,have conspired to create the ideal environment for establishing treatments for IRD,with the first approved gene therapy and the commencement of multiple therapy trials.The scope of this review is to familiarize clinicians and scientists with the current landscape of retinal imaging in IRD.Herein we present in a comprehensive and concise manner the imaging findings of:(I)macular dystrophies(MD)[Stargardt disease(ABCA4),X-linked retinoschisis(RS1),Best disease(BEST1),pattern dystrophy(PRPH2),Sorsby fundus dystrophy(TIMP3),and autosomal dominant drusen(EFEMP1)],(II)cone and cone-rod dystrophies(GUCA1A,PRPH2,ABCA4 and RPGR),(III)cone dysfunction syndromes[achromatopsia(CNGA3,CNGB3,PDE6C,PDE6H,GNAT2,ATF6],blue-cone monochromatism(OPN1LW/OPN1MW array),oligocone trichromacy,bradyopsia(RGS9/R9AP)and Bornholm eye disease(OPN1LW/OPN1MW),(IV)Leber congenital amaurosis(GUCY2D,CEP290,CRB1,RDH12,RPE65,TULP1,AIPL1 and NMNAT1),(V)rod-cone dystrophies[retinitis pigmentosa,enhanced S-Cone syndrome(NR2E3),Bietti crystalline corneoretinal dystrophy(CYP4V2)],(VI)rod dysfunction syndromes(congenital stationary night blindness,fundus albipunctatus(RDH5),Oguchi disease(SAG,GRK1),and(VII)chorioretinal dystrophies[choroideremia(CHM),gyrate atrophy(OAT)].