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Refractive errors, in particular myopia, are a leading cause of morbidity and disability worldwide. Genetic investigation can improve understanding of the molecular mechanisms that underlie abnormal eye development and impaired vision. We conducted a meta-analysis of genome-wide association studies (GWAS) that involved 542,934 European participants and identified 336 novel genetic loci associated with refractive error. Collectively, all associated genetic variants explain 18.4% of heritability and improve the accuracy of myopia prediction (area under the curve (AUC) = 0.75). Our results suggest that refractive error is genetically heterogeneous, driven by genes that participate in the development of every anatomical component of the eye. In addition, our analyses suggest that genetic factors controlling circadian rhythm and pigmentation are also involved in the development of myopia and refractive error. These results may enable the prediction of refractive error and the development of personalized myopia prevention strategies in the future.

We measured corneal sensitivity in 14 patients with infantile nephropathic cystinosis and in 13 age-matched controls. All patients with cystinosis had the pathognomonic anterior segment findings of crystal deposition within conjunctiva and cornea. Transcutaneous stimulation of the supraorbital nerve and surface electromyographic recording of the orbicularis oculi muscle performed on four patients showed a normal afferent limb to the blink reflex. The corneal sensitivity in patients with cystinosis was 3.18 g/mm2; in the control subjects it was 0.43 g/mm2. This difference was statistically significant (P < .001).

We studied 15 patients with infantile nephropathic cystinosis. We found that anterior corneal cystine crystal deposition began early in life and proceeded posteriorly as the patient aged; deposition advanced more rapidly in the periphery. Ultrastructural analysis of a corneal button obtained from a 20-year-old patient undergoing corneal transplantation confirmed our clinical observations that crystals were deposited throughout the entire central stroma.

• Cystinosis is a rare autosomal recessive metabolic disorder in which nonprotein cystine accumulates within most body organs due to a defect in lysosomal cystine transport. The pathognomonic ocular manifestations of cystinosis are the presence of distinctive iridescent crystals within ocular tissue and a pigmentary retinopathy. We measured spatial contrast sensitivity in seven patients with infantile-onset nephropathic cystinosis and compared their contrast sensitivity function with that measured in ten age-matched controls. Spatial contrast sensitivities in the patient group were significantly lower than those in the normal group. Loss of contrast sensitivity in the patients with nephropathic cystinosis was more pronounced at higher spatial frequencies. We speculate that this loss of contrast function is primarily a manifestation of corneal disease, with secondary contributions from retinal changes and central nervous system dysfunction.

Whether crystals typical of cystinosis appear within the corneal stroma of a donor button transplanted into the eye of a patient with nephropathic cystinosis has become controversial.1-3 We described a patient who had bilateral penetrating keratoplasties and nephropathic cystinosis, and who—when examined some 6 weeks after transplant—exhibited crystals typical of cystinosis within his donor button.1 The same patient examined elsewhere 10 months after transplantation was described as having a clear corneal graft.2 We had the opportunity to examine another patient with nephropathic cystinosis who also underwent penetrating keratoplasty and again to document the recurrence of corneal crystal deposition within a donor button. REPORT OF A CASE. —A 19-year-old woman with juvenile nephropathic cystinosis underwent two renal allografts. Her systemic medications included prednisone and azathioprine. Ophthalmic evaluation documented characteristic crystals of cystinosis within the conjunctiva and cornea. She presented with presumed pupillary block glaucoma of the left eye.

• Cystinosis is a rare metabolic disorder in which nonprotein cystine accumulates within lysosomes due to a defect in lysosomal cystine transport. Although cystine accumulates within most ocular tissues, patients with cystinosis generally complain only of photophobia and glare. We measured glare sensitivity in 12 patients with infantile cystinosis and compared their results with an age-matched control population. Ten of the 12 patients with cystinosis had demonstrable glare disability when compared with the control group. Glare disability scores in the patients with cystinosis ranged from 5% to 50%. Dazzle glare resulting from the accumulation of cystine crystals in ocular tissue may account for glare disability seen in these patients and contribute to their complaints of photophobia.

• Cystinosis is an autosomal recessive metabolic disorder in which nonprotein cystine accumulates within most body tissues due to a defect in lysosomal cystine transport. Neurologic declarations are only recently being recognized. We studied 13 cystinotic subjects (aged 5 to 21 years old), determining median motor and sensory nerve conduction velocities, F waves, peroneal motor nerve conduction velocities, sural sensory nerve conduction velocities, median sympathetic skin response, electrocardiogram R-to-R variability, and blink reflex analysis. The results were normal. We conclude that neurophysiologic testing suggests relative sparing of the peripheral nervous system in nephropathic cystinosis.