Biometric and molecular characterization of clinically diagnosed posterior microphthalmos

To biometrically and molecularly characterize clinically diagnosed posterior microphthalmos.

Prospective case series.

Twenty-five affected patients from 13 families diagnosed by ophthalmologists experienced with the condition at the King Khaled Eye Specialist Hospital were studied. All participants underwent axial length measurement, keratometry, corneal pachymetry, and candidate gene analysis (MFRP, PRSS56). Main outcome measures were the results of ocular biometry and gene analysis.

All patients (2-47 years of age) had high hyperopia, normal-appearing anterior segments, posterior chamber foreshortening, and characteristic papillomacular folds/wrinkles. For the right eye, mean cycloplegic refraction was +15.09 diopters (D) (range 9.88-18.75). Axial length (mean 16.25 mm [range 14.88-19.88]) had strong inverse correlation (Pearson coefficient -0.88, P < .0001) with corneal power (mean 48.89 D [range 41.91-52.25]) and a positive correlation with corneal diameter (Pearson 0.64, P = .001). Corneal thickness and anterior chamber dimensions were within normal ranges. Left eye data were similar. Nineteen Saudi patients (8/13 families) harbored 4 different homozygous PRSS56 mutations, 1 Indian and 1 Saudi patient harbored 2 different homozygous MFRP mutations, and 4 Saudi patients (3/13 families) had no detectable mutation in either gene. Patients with MFRP mutations were not clinically different from patients with PRSS56 mutations or no identified mutation. Truncating PRSS56 mutations were associated with shorter axial lengths (mean 15.72 mm) than missense PRSS56 mutations (mean 16.37 mm) or no identified mutation (mean 17.57 mm).

These data define posterior microphthalmos biometrically and reveal that corneal steepening proportional to the degree of axial foreshortening is part of the phenotype. Corneal diameter decreases with decreasing axial length, suggesting posterior microphthalmos and nanophthalmos represent a spectrum of high hyperopia rather than distinct phenotypes. In the Saudi population PRSS56 mutations are the major cause, and in our cohort truncating mutations were associated with a more severe phenotype.