PURPOSE: Posterior corneal vesicles (PCVs) have clinical features that are similar to posterior polymorphous corneal dystrophy (PPCD). To help determine whether there is a shared genetic basis, we screened 38 individuals with PCVs for changes in the three genes identified as causative for PPCD. METHODS: We prospectively recruited patients for this study. We examined all individuals clinically, with their first-degree relatives when available. We used a combination of Sanger and exome sequencing to screen regulatory regions of OVOL2 and GRHL2, and the entire ZEB1 coding sequence. RESULTS: The median age at examination was 37.5 years (range 4.7-84.0 years), 20 (53%) were male and in 19 (50%) the PCVs were unilateral. Most individuals were discharged to optometric review, but five had follow-up for a median of 12 years (range 5-13 years) with no evidence of progression. In cases with unilateral PCVs, there was statistically significant evidence that the change in the affected eye was associated with a lower endothelial cell density (p = 0.0003), greater central corneal thickness (p = 0.0277) and a steeper mean keratometry (p = 0.0034), but not with a higher keratometric astigmatism or a reduced LogMAR visual acuity. First-degree relatives of 13 individuals were available for examination, and in 3 (23%), PCVs were identified. No possibly pathogenic variants were identified in the PPCD-associated genes screened. CONCLUSION: We found no evidence that PCVs share the same genetic background as PPCD. In contrast to PPCD, we confirm that PCVs is a mild, non-progressive condition with no requirement for long-term review. However, subsequent cataract surgery can lead to corneal oedema.

Department of Computer Science Czech Technical University Prague Prague Czech Republic

Department of Ophthalmology 1st Faculty of Medicine Charles University and General University Hospital Prague Prague Czech Republic

Department of Paediatrics and Inherited Metabolic Disorders 1st Faculty of Medicine Charles University and General University Hospital Prague Prague Czech Republic

Moorfields Eye Hospital London UK

UCL Institute of Ophthalmology London UK

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Aldave AJ, Ann LB, Frausto RF, Nguyen CK, Yu F & Raber IM (2013): Classification of posterior polymorphous corneal dystrophy as a corneal ectatic disorder following confirmation of associated significant corneal steepening. JAMA Ophthalmol 131: 1583-1590.

Aldave AJ, Yellore VS, Yu F et al. (2007): Posterior polymorphous corneal dystrophy is associated with TCF8 gene mutations and abdominal hernia. Am J Med Genet A 143A: 2549-2556.

Cibis GW, Krachmer JA, Phelps CD & Weingeist TA (1977): The clinical spectrum of posterior polymorphous dystrophy. Arch Ophthalmol 95: 1529-1537.

Cibis GW & Tripathi RC (1982): The differential diagnosis of Descemet's tears (Haab's striae) and posterior polymorpous dystrophy bands. A clinicopathologic study. Ophthalmology 89: 614-620.

Davidson AE, Liskova P, Evans CJ et al. (2016): Autosomal-dominant corneal endothelial dystrophies CHED1 and PPCD1 are allelic disorders caused by non-coding mutations in the promoter of OVOL2. Am J Hum Genet 98: 75-89.

Dudakova L, Evans CJ, Pontikos N et al. (2019): The utility of massively parallel sequencing for posterior polymorphous corneal dystrophy type 3 molecular diagnosis. Exp Eye Res 182: 160-166.

Dudakova L, Stranecky V, Piherova L et al. (2021): Non-penetrance for ocular phenotype in two individuals carrying heterozygous loss-of-function ZEB1 alleles. Genes (Basel) 12: 677-684.

Evans CJ, Liskova P, Dudakova L et al. (2015): Identification of six novel mutations in ZEB1 and description of the associated phenotypes in patients with posterior polymorphous corneal dystrophy 3. Ann Hum Genet 79: 1-9.

Harada T, Tanaka H, Ikema T, Asakura K, Miura M & Ozeki Y (1990): Specular microscopic observation of posterior corneal vesicles. Ophthalmologica 201: 122-127.

Henriquez AS, Kenyon KR, Dohlman CH, Boruchoff SA, Forstot SL, Meyer RF & Hanninen LA (1984): Morphologic characteristics of posterior polymorphous dystrophy. A study of nine corneas and review of the literature. Surv Ophthalmol 29: 139-147.

Jirsova K, Merjava S, Martincova R, Gwilliam R, Ebenezer ND, Liskova P & Filipec M (2007): Immunohistochemical characterization of cytokeratins in the abnormal corneal endothelium of posterior polymorphous corneal dystrophy patients. Exp Eye Res 84: 680-686.

Kitazawa K, Hikichi T, Nakamura T et al. (2016): OVOL2 maintains the transcriptional program of human corneal epithelium by suppressing epithelial-to-mesenchymal transition. Cell Rep 15: 1359-1368.

Krachmer JH (1985): Posterior polymorphous corneal dystrophy: a disease characterized by epithelial-like endothelial cells which influence management and prognosis. Trans Am Ophthalmol Soc 83: 413-475.

Krafchak CM, Pawar H, Moroi SE et al. (2005): Mutations in TCF8 cause posterior polymorphous corneal dystrophy and ectopic expression of COL4A3 by corneal endothelial cells. Am J Hum Genet 77: 694-708.

Laganowski HC, Sherrard ES & Muir MG (1991): The posterior corneal surface in posterior polymorphous dystrophy: a specular microscopical study. Cornea 10: 224-232.

Levenson JE, Chandler JW & Kaufman HE (1973): Affected asymptomatic relatives in congenital hereditary endothelial dystrophy. Am J Ophthalmol 76: 967-971.

Liskova P, Dudakova L, Evans CJ et al. (2018): Ectopic GRHL2 expression due to non-coding mutations promotes cell state transition and causes posterior polymorphous corneal dystrophy 4. Am J Hum Genet 102: 447-459.

Liskova P, Palos M, Hardcastle AJ & Vincent AL (2013): Further genetic and clinical insights of posterior polymorphous corneal dystrophy 3. JAMA Ophthalmol 131: 1296-1303.

Liskova P, Tuft SJ, Gwilliam R et al. (2007): Novel mutations in the ZEB1 gene identified in Czech and British patients with posterior polymorphous corneal dystrophy. Hum Mutat 28: 638.

Malbran ES (1972): Corneal dystrophies: a clinical, pathological, and surgical approach. 28 Edward Jackson Memorial Lecture. Am J Ophthalmol 74: 771-809.

McKenna A, Hanna M, Banks E et al. (2010): The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res 20: 1297-1303.

Noguchi A, Okumura N, Sotozono C & Kinoshita S (2018): Effect of posterior corneal vesicles on corneal endothelial cell density and anisometropic amblyopia. Cornea 37: 813-817.

Pardos GJ, Krachmer JH & Mannis MJ (1981): Posterior corneal vesicles. Arch Ophthalmol 99: 1573-1577.

Patel DV, Grupcheva CN & McGhee CN (2005): In vivo confocal microscopy of posterior polymorphous dystrophy. Cornea 24: 550-554.

Raber IM, Fintelmann R, Chhabra S, Ribeiro MP, Eagle RC Jr & Orlin SE (2011): Posterior polymorphous dystrophy associated with nonkeratoconic steep corneal curvatures. Cornea 30: 1120-1124.

Shiraishi A, Zheng X, Sakane Y, Hara Y & Hayashi Y (2016): In vivo confocal microscopic observations of eyes diagnosed with posterior corneal vesicles. Jpn J Ophthalmol 60: 425-432.

Vincent AL, Niederer RL, Richards A, Karolyi B, Patel DV & McGhee CN (2009): Phenotypic characterisation and ZEB1 mutational analysis in posterior polymorphous corneal dystrophy in a New Zealand population. Mol Vis 15: 2544-2553.

Waring GO 3rd, Rodrigues MM & Laibson PR (1978): Corneal dystrophies. II Endothelial dystrophies. Surv Ophthalmol 23: 147-168.

Watanabe R, Nakazawa T & Fuse N (2010): Observation of posterior corneal vesicles with in vivo confocal microscopy and anterior segment OCT. Clin Ophthalmol 4: 1243-1247.

Weiss JS, Møller HU, Aldave AJ et al. (2015): IC3D classification of corneal dystrophies--edition 2. Cornea 34: 117-159.

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