Clinical pathological correlations in Meretoja corneal lattice amyloidosis

Abstract

AbstractCorneal lattice amyloidosis, previously mis‐designated lattice corneal dystrophy, type II, is the earliest clinical manifestation of gelsolin amyloidosis (Agel), also known as Meretoja syndrome and Familial amyloidosis, Finnish. Agel results from one of two single nucleotide substitutions in gelsolin gene. Although most common in Finland, Agel is found in several countries in North America, Europe, and Asia. We analysed the outcome of penetrating keratoplasty (PK) and distribution of corneal amyloid in a retrospective series of 31 patients (median follow‐up, 32 months). At 2 years after PK, median BCVA was 20/280 versus 20/400 preoperatively; 3/18 eyes had a BCVA ≥20/63 and 13/18 grafts were clear. Graft failed in 16/31 eyes, which resulted from surface complications in 11/16 eyes; 7 eyes were re‐grafted. Corneal neovascularization predicted failure and poor BCVA. To correlate visual results with amyloid deposition, we stained PK specimens from 42 patients with Congo red, and digitally labelled amyloid deposits and stromal tissue on pixel level for training and validation of an automated algorithm to quantify relative amyloid deposition (RAD) and its association with BCVA. Areas of amyloid and stroma detected by the algorithms were displayed on whole slide images (WSI) with a red overlay. We had not enough evidence to either prove or exclude a correlation (Spearman's rank correlation, −0.264, p = 0.091) between RAD and BCVA. It may be that deposition of amyloid in an around Bowman layer rather than the total RAD in the cornea determines the outcome after PK. Because of the failure risk and guarded visual prognosis after PK in Agel, it is reasonable to limit PK to bilateral advanced disease and try to optimize ocular surface health to delay PK.