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Abstract-The purpose of this study was to investigate the long-term visual dysfunction in patients after blast-induced mild traumatic brain injury (mbTBI) using a retrospective case series of 31 patients with mbTBI (>12 mo prior) without eye injuries. Time since mbTBI was 50.5 +/-19.8 mo. Age at the time of injury was 30.0 +/-8.3 yr. Mean corrected visual acuity was 20/20. Of the patients, 71% (n = 22) experienced loss of consciousness; 68% (n = 15) of patients in this subgroup were dismounted during the blast injury. Overall, 68% (n = 21) of patients had visual complaints. The most common complaints were photophobia (55%) and difficulty with reading (32%). Of all patients, 25% were diagnosed with convergence insufficiency and 23% had accommodative insufficiency. Patients with more than one mbTBI had a higher rate of visual complaints (87.5%). Asymptomatic patients had a significantly longer time (62.5 +/-6.2 mo) since the mbTBI than symptomatic patients (42.0 +/-16.4 mo, p < 0.004). Long-term visual dysfunction after mbTBI is common even years after injury despite excellent distance visual acuity and is more frequent if more than one incidence of mbTBI occurred. We recommend obtaining a careful medical history, evaluation of symptoms, and binocular vision assessment during routine eye examinations in this prepresbyopic patient population.Key words: accommodative insufficiency, blast-induced traumatic brain injury, combat-related traumatic brain injury, convergence insufficiency, dismounted injury, eyes, loss of consciousness, mild traumatic brain injury, near vision deficit, photophobia, traumatic brain injury, visual dysfunction.

γ-crystallins constitute the major protein component in the nucleus of the vertebrate eye lens. Present at very high concentrations, they exhibit extreme solubility and thermodynamic stability to prevent scattering of light and the formation of cataracts. However, functions beyond this structural role have remained mostly unclear. Here, we calculate molecular refractive index increments of crystallins. We show that all lens γ-crystallins have evolved a significantly elevated molecular refractive index increment, which is far above those of most proteins, including non-lens members of the βγ-crystallin family from different species. The same trait has evolved in parallel in crystallins of different phyla, including in the S-crystallins of cephalopods. A high refractive index increment can lower the crystallin concentration required to achieve a suitable refractive power of the lens, and thereby reduce their propensity to aggregate and form cataract. To produce a significant increase of the refractive index increment, a substantial global shift in the amino acid composition is required, which can naturally explain the highly unusual amino acid composition of γ-crystallins and their functional homologues. This function provides a new perspective for interpreting their molecular structure.

Crystallins are present in the lens at extremely high concentrations in order to provide transparency and generate a high refractive power of the lens. The crystallin families prevalent in the highest density lens tissues are γ crystallins in vertebrates and S crystallins in cephalopods. In parallel evolution, both have evolved molecular refractive index increments 5 – 10 % above those of most proteins. Although this is a small increase, it is statistically very significant and can be achieved only by very unusual amino acid compositions. In contrast, such a molecular adaptation to aid in the refractive function of the lens did not occur in crystallins that are preferentially located in lower density lens tissues, such as vertebrate α crystallin and taxon specific crystallins. In the current work, we apply a model of non-interacting hard spheres to examine the thermodynamic contributions of volume exclusion at lenticular protein concentrations. We show that the small concentration decrease afforded by the higher molecular refractive index increment of crystallins can amplify nonlinearly to produce order of magnitude differences in chemical activities, and lead to reduced osmotic pressure and the reduced propensity for protein aggregation. Quantitatively, this amplification sets in only at protein concentrations as high as those found in hard lenses or the nucleus of soft lenses, in good correspondence to the observed crystalline properties in different tissues and different species. This suggests that volume exclusion effects provide the evolutionary driving force for the unusual refractive properties and the unusual amino acid compositions of γ crystallins and S crystallins.