Distribution and Surgical Treatment of Corneal Dystrophies Over Eight Decades (1945-2024): An Analysis of Histopathologically Confirmed Cases from a German Center

Abstract

Background: Corneal dystrophies are inherited disorders that can lead to significant visual impairment and often require surgical intervention in advanced stages. Fuchs endothelial corneal dystrophy (FECD) is the most frequently diagnosed type in Western countries and remains a leading global indication for corneal transplantation. In contrast, non-Fuchs dystrophies represent a diverse group of less common entities, each with distinct clinical features, surgical considerations, and regional variations in incidence and management. Despite their relevance, long-term data on the full spectrum of corneal dystrophies remain scarce. This study aimed to evaluate the distribution and temporal trends in dystrophy types and associated surgical procedures over eight decades at a tertiary referral center in Germany.

Methods: This retrospective analysis included 3 827 histopathologically confirmed corneal dystrophy specimens identified from an archive of 58 150 ophthalmic specimens collected between 1945 and 2024. Extracted data included dystrophy type, patient age at surgery, sex assigned at birth and associated surgical procedures. Distribution and temporal trends were analyzed descriptively.

Results: FECD accounted for 90.3% (n = 3 455) of all cases, with a more than 15-fold increase in annual cases between 2003 and 2024. Its surgical management transitioned from exclusive use of penetrating keratoplasty (PKP) to posterior lamellar keratoplasty in over 99% of cases by 2024. Among non-Fuchs dystrophies (n = 372), granular (21.2%), macular (17.5%), and lattice dystrophy (17.2%) were most frequent. These exhibited greater surgical variability, reflecting their heterogeneity across 21 non-Fuchs dystrophy types in this study. Stromal and epithelial-stromal dystrophies were predominantly managed with PKP, whereas superficial epithelial and basement membrane dystrophies were increasingly treated with phototherapeutic or manual superficial keratectomy. Limbo-keratoplasty was introduced in the early 2000s for recurrent subepithelial and epithelial-stromal types.

Conclusion: This study provides unique insights into the type distribution and surgical management of corneal dystrophies over eight decades in a German center, encompassing nearly all IC3D-classified entities. The marked increase in FECD specimen numbers and the shift toward lamellar keratoplasty reflect evolving clinical practices and rising demand on corneal transplantation services. The broader clinical spectrum and procedural diversity among non-Fuchs dystrophies underscore the ongoing need for pathology-specific management strategies tailored to population-specific needs.

Keywords: Cornea; Corneal dystrophies; Histopathology; Keratoplasty; Longitudinal study; Ocular epidemiology; Ophthalmic pathology; Surgical trends; Transplantation.

Fig. 1

Annual distribution of histopathologically confirmed Fuchs (n = 3455) and non-Fuchs corneal dystrophies (n = 372) No corneal dystrophies were diagnosed between 1945 and 1965, although corneal specimens from that period exist in the archive. For this reason, the x-axis begins in 1966

Fig. 2

Annual distribution of histopathologically confirmed non-Fuchs dystrophies (n = 372) Dystrophies are grouped into four categories. Granular (all types): Granular corneal dystrophy (n = 79), all types; Lattice: Lattice corneal dystrophy (n = 64); Macular: Macular corneal dystrophy (n = 65); Others: other less frequent non-Fuchs corneal dystrophies (n = 164)

Fig. 3

Temporal trends in surgical procedures for Fuchs Endothelial Corneal Dystrophy specimens (n = 3455) Annual distribution of surgical procedures associated with histopathologically confirmed Fuchs endothelial corneal dystrophy specimens. Posterior Lamellar Keratoplasty: Descemet stripping endothelial keratoplasty (DSAEK) and Descemet membrane endothelial keratoplasty (DMEK); Enucleation: enucleated eyes submitted postmortem or from living patients, for comprehensive histopathological examination, including corneal evaluation

Fig. 4

Temporal trends in surgical procedures for non-Fuchs dystrophy specimens (n = 372) Annual distribution of surgical procedures associated with histopathologically confirmed non-Fuchs corneal dystrophy specimens. PKP: penetrating keratoplasty; LimboKP: limbo-keratoplasty; Postmortem enucleation: the entire eye was obtained postmortem for histopathological examination; DMEK: descemet membrane endothelial keratoplasty; MSK: manual superficial keratectomy; PTK: phototherapeutic keratectomy

Fig. 5

Distribution of surgical procedures by dystrophy type for non-Fuchs dystrophy specimens (n = 372) Overview of surgical procedures associated with each histopathologically confirmed corneal dystrophy type. PKP: penetrating keratoplasty; LimboKP: limbo-keratoplasty; DMEK: descemet membrane endothelial keratoplasty; MSK: manual superficial keratectomy; PTK: phototherapeutic keratectomy; Postmortem enucleation: the entire eye was obtained postmortem for histopathological examination; EBMD: Epithelial basement membrane dystrophy; ERED: Epithelial recurrent erosion dystrophy; Franceschetti: Franceschetti corneal dystrophy; SMCD: Subepithelial mucinous corneal dystrophy; Meesmann: Meesmann corneal dystrophy; Lisch: Lisch epithelial corneal dystrophy; Gelatinous: Gelatinous drop-like corneal dystrophy; RBCD: Reis–Bücklers corneal dystrophy; TBCD: Thiel–Behnke corneal dystrophy; Lattice: Lattice corneal dystrophy; GCD: Granular corneal dystrophy – unspecified type; GCD1: Granular corneal dystrophy, type 1; GCD2: Granular corneal dystrophy, type 2; Gly, Glycin; Asp, Aspartic acid amino acid; Gly623Asp: corneal dystrophy associated with missense mutation in exon 14 of the TGFBI gene (G->A transition at nucleotide 1915) replacing glycin by aspartic acid amino acid at position 623; Macular: Macular corneal dystrophy; Schnyder: Schnyder corneal dystrophy; CSCD: Congenital stromal, Congenital stromal corneal dystrophy; PACD: Posterior amorphous corneal dystrophy; Pre-Descemet: Pre-Descemet corneal dystrophy; PPCD: Posterior polymorphous corneal dystrophy; CHED: Congenital hereditary endothelial dystrophy; Epithelial CD: unspecified epithelial corneal dystrophy; Epithelial-stromal CD: unspecified epithelial-stromal corneal dystrophy; Stromal CD: unspecified stromal corneal dystrophy; Endothelial CD: unspecified endothelial corneal dystrophy; Unspecified: localization and type of the dystrophy not specified. Three specimens initially treated with PKP (two diagnosed as lattice dystrophy and one as an unspecified epithelial-stromal dystrophy) were later reclassified as Gly623Asp mutation variants. For consistency, they are presented in the figure under their original diagnostic categories