Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic, premalignant disease with a progression rate of 0.5%-1% per year to multiple myeloma. It can rarely present with significant ocular symptoms in the context of crystalline keratopathy, necessitating medical and surgical interventions. Lattice corneal dystrophy Type I (LCD-1), a rare inherited disorder caused by mutations of TGFBI, manifests with amyloid deposition within the corneal stroma and causes visual impairment. Here, we pictorially highlight protein deposition using immunofluorescence in two representative cases, both having undergone penetrating keratoplasty for blurry vision. Medical records were reviewed. Hematoxylin and eosin, special staining, immunohistochemistry, and immunofluorescent techniques were performed. A literature review was performed. Case 1: Eosinophilic accumulations of the cornea were highlighted with PAS-D and IgG-kappa by immunohistochemistry, whereas immunofluorescence (IF) technique demonstrated IgG-kappa (2+) staining in the stroma with rare globules in the epithelium. Case 2: Amorphous, eosinophilic deposits within the corneal stroma were congophilic with apple-green birefringence on polarized light. Thioflavin T highlighted the amyloid through immunofluorescence. Mass spectrometry detected a peptide profile consistent with ATGFBI-type amyloid deposition. Immunofluorescence can be helpful in the workup of corneal protein deposition, such as MGUS-related crystalline keratopathy and LCD-1.

Lattice corneal dystrophy Type I (LCD1) is characterized by amyloid deposition in the corneal stroma, however its impact on Descemet's membrane adhesion remains poorly understood. This study reports a rare case of Descemet's membrane detachment (DMD) during cataract surgery in a patient with LCD1 and investigates the potential role of posterior corneal amyloid deposits in this complication. A 68-year-old male presented with LCD1 was admitted for cataract surgery for the left eye. DMD appeared during the irrigation and aspiration (I/A) phase after intraocular lens (IOL) implantation. After intraoperative partial removal of DM, persistent Descemet's membrane folds and corneal stromal edema developed the day after surgery. These complications did not improve over time, necessitating penetrating keratoplasty eight months later. Following the keratoplasty, the patient's vision improved to 0.5 LogMAR with an uneventful postoperative course. Pathological examination of the excised corneal tissue demonstrated the presence of Congo red stain-positive amyloid deposits in the posterior segment of the cornea, localized between the layers of Descemet's membrane and the corneal stroma. While it is established that amyloid deposition in the anterior segment of the cornea induces alterations in epithelial adhesion, leading to corneal erosions, the effects of deposits on DM adhesion in the posterior segment are yet to be fully understood. Our case's pathological findings suggested that these deposits may contribute to DMD. Therefore, careful monitoring of DM is crucial during cataract surgical interventions in patients diagnosed with LCD1.

To identify a clinical and genetic form of a large Chinese family with an autosomal-dominant lattice corneal dystrophy type I (LCD I). The patients' eyes were examined on the basis of slit-lamp microscopy, and other clinical records were also collected. Genomic DNA was extracted from peripheral leukocytes of the affected patients and their unaffected family members. Each previous reported mutation of the transforming growth factor β-induced gene (TGFBI) gene was amplified by touch-down polymerase chain reaction and directly sequenced to verify the disease-causing mutation. Typical clinical features of LCD I were found by slit-lamp photography in these affected Chinese pedigrees. A heterozygous single base-pair transition from C to T (c.418 C > T), leading to amino acid substitution Arg124Cys (R124C) in the encoded TGFBI protein, was detected in all of the eighteen affected patients. The same mutation was not found in unaffected family members. The R124C mutation hot spot, which was relatively rare in China, was responsible for LCD I in the large family. Molecular genetic analysis of TGFBI gene can offer an accurate diagnosis of patients with lattice corneal dystrophies in the clinical treatment.

To identify the types of TGFBI (transforming growth factor, beta-induced) gene mutations in three Chinese families with Reis-Bücklers corneal dystrophy (RBCD), lattice corneal dystrophy type I (LCDI), or Avellino corneal dystrophy (ACD) and to investigate the relationship between the phenotypes and genotypes of corneal dystrophy. Peripheral blood was collected from 24 patients and 76 phenotypically normal members in three Chinese families as well as from 100 healthy controls. Genomic DNA was extracted. All 17 exons of the TGFBI gene, and the exon-intron junctions were examined by polymerase chain reaction (PCR) and direct DNA sequencing to identify and analyse gene mutations. In addition, all members of the three families were subjected to detailed clinical examinations. The heterozygous c.371G > T (p.R124L) mutation was detected in exon 4 of the TGFBI gene in nine patients from the family with RBCD. In contrast, this mutation was not found in the phenotypically normal members of the family. The heterozygous c.370C > T (p.R124C) mutation was found in exon 4 of the TGFBI gene in 11 patients from the family with LCDI. This mutation was not found in the phenotypically normal members of the family. The heterozygous c.371G > A (p.R124H) mutation was detected in exon 4 of the TGFBI gene in four patients from the family with ACD. Again, this mutation was not found in the phenotypically normal members of the family. The TGFBI gene mutations cosegregated with the disease phenotypes in the three families and exhibited an autosomal dominant mode of inheritance. No TGFBI gene mutations were detected in the 100 healthy controls. There is a high degree of correlation between the phenotypes and genotypes of TGFBI-linked corneal dystrophies. R124 represents a mutational hotspot in the TGFBI gene. Gene mutation analysis provides a reliable basis for the definitive diagnosis of corneal dystrophy.

Lattice corneal dystrophy type I (LCDI) is associated with a large number of missense mutations in the transforming growth factor β induced (TGFBI) gene. The aim of the present study was to analyze TGFBI mutation in a Chinese family with LCDI, and to describe the clinical features and phenotype-genotype correlation within this family. Three generations of this family with LCDI were enrolled in the current study. Complete ophthalmic examinations were performed on all family members and mutation screenings of the coding regions of TGFBI were analyzed using a direct sequencing method. All family members underwent slit-lamp examination, and two patients and one of normal members in the family were evaluated by laser scanning in vivo confocal microscopy. A single heterozygous c.370C>T (p.R124C) mutation was identified in exon 4 of the TGFBI gene in five affected individuals, but not in the other family members and 400 normal control subjects. The affected members exhibited similar clinical features of LCDI, except that patient III:5 presented with mild symptoms. Confocal microscopy in vivo examination demonstrated that the proband (II:2) and his affected niece (III:4) had disruptions in multiple corneal layers, including the basal epithelial cells, stroma cells and Bowman's membrane. Thus, the R124C mutation in the TGFBI gene was identified in a Chinese family with LCDI. These results characterized the clinical features and revealed a genotype-associated phenotype in this family, which may contribute to understanding the pathogenesis of LCDI.