A medieval fallacy: the crystalline lens in the center of the eye.

OBJECTIVE: To determine whether, as most modern historians have written, ancient Greco-Roman authors believed the crystalline lens is positioned in the center of the eye. BACKGROUND: Historians have written that statements about cataract couching by Celsus, or perhaps Galen of Pergamon, suggested a centrally located lens. Celsus specifically wrote that a couching needle placed intermediate between the corneal limbus and the lateral canthus enters an empty space, presumed to represent the posterior chamber. METHODS: Ancient ophthalmic literature was analyzed to understand where these authors believed the crystalline lens was positioned. In order to estimate where Celsus proposed entering the eye during couching, we prospectively measured the distance from the temporal corneal limbus to the lateral canthus in 30 healthy adults. RESULTS: Rufus of Ephesus and Galen wrote that the lens is anterior enough to contact the iris. Galen wrote that the lens equator joins other ocular structures at the corneoscleral junction. In 30 subjects, half the distance from the temporal corneal limbus to the lateral canthus was a mean of 4.5 mm (range: 3.3-5.3 mm). Descriptions of couching by Celsus and others are consistent with pars plana entry of the couching needle. Anterior angulation of the needle would permit contact of the needle with the lens. CONCLUSION: Ancient descriptions of anatomy and couching do not establish the microanatomic relationships of the ciliary region with any modern degree of accuracy. Nonetheless, ancient authors, such as Galen and Rufus, clearly understood that the lens is located anteriorly. There is little reason to believe that Celsus or other ancient authors held a variant understanding of the anatomy of a healthy eye. The notion of the central location of the lens seems to have arisen with Arabic authors in 9th century Mesopotamia, and lasted for over 7 centuries.

The early history of glaucoma: the glaucous eye (800 BC to 1050 AD).

To the ancient Greeks, glaukos occasionally described diseased eyes, but more typically described healthy irides, which were glaucous (light blue, gray, or green). During the Hippocratic period, a pathologic glaukos pupil indicated a media opacity that was not dark. Although not emphasized by present-day ophthalmologists, the pupil in acute angle closure may appear somewhat green, as the mid-dilated pupil exposes the cataractous lens. The ancient Greeks would probably have described a (normal) green iris or (diseased) green pupil as glaukos. During the early Common Era, eye pain, a glaucous hue, pupil irregularities, and absence of light perception indicated a poor prognosis with couching. Galen associated the glaucous hue with a large, anterior, or hard crystalline lens. Medieval Arabic authors translated glaukos as zarqaa, which also commonly described light irides. Ibn Sina (otherwise known as Avicenna) wrote that the zarqaa hue could occur due to anterior prominence of the lens and could occur in an acquired manner. The disease defined by the glaucous pupil in antiquity is ultimately indeterminate, as the complete syndrome of acute angle closure was not described. Nonetheless, it is intriguing that the glaucous pupil connoted a poor prognosis, and came to be associated with a large, anterior, or hard crystalline lens.

ADAM8 enhances osteoclast precursor fusion and osteoclast formation in vitro and in vivo.

ADAM8 expression is increased in the interface tissue around a loosened hip prosthesis and in the pannus and synovium of patients with rheumatoid arthritis, but its potential role in these processes is unclear. ADAM8 stimulates osteoclast (OCL) formation, but the effects of overexpression or loss of expression of ADAM8 in vivo and the mechanisms responsible for the effects of ADAM8 on osteoclastogenesis are unknown. Therefore, to determine the effects of modulating ADAM expression, we generated tartrate-resistant acid phosphatase (TRAP)-ADAM8 transgenic mice that overexpress ADAM8 in the OCL lineage and ADAM8 knockout (ADAM8 KO) mice. TRAP-ADAM8 mice developed osteopenia and had increased numbers of OCL precursors that formed hypermultinucleated OCLs with an increased bone-resorbing capacity per OCL. They also had an enhanced differentiation capacity, increased TRAF6 expression, and increased NF-κB, Erk, and Akt signaling compared with wild-type (WT) littermates. This increased bone-resorbing capacity per OCL was associated with increased levels of p-Pyk2 and p-Src activation. In contrast, ADAM8 KO mice did not display a bone phenotype in vivo, but unlike WT littermates, they did not increase RANKL production, OCL formation, or calvarial fibrosis in response to tumor necrosis factor α (TNF-α) in vivo. Since loss of ADAM8 does not inhibit basal bone remodeling but only blocks the enhanced OCL formation in response to TNF-α, these results suggest that ADAM8 may be an attractive therapeutic target for preventing bone destruction associated with inflammatory disease.

The instant axis of rotation influences facet forces at L5/S1 during flexion/extension and lateral bending.

Because the disc and facets work together to constrain spinal kinematics, changes in the instant axis of rotation associated with disc degeneration or disc replacement may adversely influence risk for facet overloading and arthritis. The relationships between L5/S1 segmental kinematics and facet forces are not well defined, since previous studies have separated investigations of spinal motion and facet force. The goal of this cadaveric biomechanical study was to report and correlate a measure of intervertebral kinematics (the centrode, or the path of the instant axis of rotation) and the facet forces at the L5/S1 motion segment while under a physiologic combination of compression and anterior shear loading. Twelve fresh-frozen human cadaveric L5/S1 joints (age range 50-64 years) were tested biomechanically under semi-constrained conditions by applying compression plus shear forces in several postures: neutral, and 3 degrees and 6 degrees of flexion, extension and lateral bending. The experimental boundary conditions imposed compression and shear representative of in vivo conditions during upright stance. The 3-D instantaneous axis of rotation (IAR) was calculated between two consecutive postures. The facet joint force was simultaneously measured using thin-film sensors placed between both facet surfaces. Variations of IAR location and facet force during motion were analyzed. During flexion and extension, the IAR was oriented laterally. The IAR intersection with the mid-sagittal plane moved cephalad relative to S1 endplate during flexion (P=0.010), and posterior during extension (P=0.001). The facet force did not correlate with posture (P=0.844). However, changes in the facet force between postures did correlate with IAR position: higher IAR's during flexion correlated with lower facet forces and vice versa (P=0.04). During lateral bending, the IAR was oblique relative to the main plane of motion and translated parallel to S1 endplate, toward the side of the bending. Overall, the facet force was increased on the ipsilateral side of bending (P=0.002). The IAR positions demonstrate that the L5 vertebral body primarily rotates forward during flexion (IAR close to vertebral body center) and rotates/translates backward during extension (IAR at or below the L5/S1 intervertebral disc). In lateral bending, the IAR obliquity demonstrated coupling with axial torsion due to resistance of the ipsilateral facet.