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Purpose: To study orthograde axonal transport with amyloid precursor protein (APP-A4) immunohistochemistry (IHC) in the retina and lamina cribrosa (LC) portion of the optic nerve in abusive head trauma (AHT) suspects., Design: Retrospective, case-control study., Methods: Seventy-two eyes from suspected AHT victims referred by the Los Angeles Coroner and control eyes from nontraumatized infants were included. IHC was conducted using University of California, Irvine (UCI), Lab Medicine Department's standard protocol and results analyzed by light microcopy after paraffin processing. Quantitation of LC APP-A4 block was estimated in 21 cases with known survival using MetaMorph, a proprietary biomicroscopy imaging software., Results: The presence or absence of APP-A4 label accumulations in retinal ganglion cells, nerve fiber layer at the disc margin, and in LC axonal bundles were compared to matching tissues from nontraumatized control eyes with only background staining. Among the globes from AHT suspects with nerve heads available for study, 94% were positive for LC accumulation of marker. Among suspect AHT cases with known survival after injury of 1 to 1588 days, most demonstrated LC APP-A4 accumulations., Conclusions: Our findings reinforce a recent publication based on APP-A4 IHC that demonstrated similar orthograde axonal transport block in the LC in children with AHT and recommend that intraocular pressures be recorded and addressed in these patients., (Copyright © 2022 Elsevier Inc. All rights reserved.) more...

Glaucoma is the second most common cause of blindness worldwide, leading to irreversible loss of vision. Prior studies indicate that ocular pressure-induced displacement of the lamina cribrosa (LC) may be responsible for retinal ganglion cell axon damage inside the neural canal. We present a novel approach to imaging the entire lamina cribrosa and the scleral canal at high lateral and axial resolution by using a combination of array tomography and nonlinear optical imaging of serial ultrathin orthogonal sections to detect second harmonic generated (SHG) signals from collagen. The resulting images can be analyzed individually or combined to form a three-dimensional reconstruction of the lamina. Due to the specificity of SHG generated from collagen the density and distribution of collagen inside the scleral canal can be objectively quantified with a high degree of accuracy. The reconstruction shows a non-uniform distribution of collagen along both the longitudinal and orthogonal axes. Mapping the collagen density by geographic region reveals significant differences in collagen content that result in "thin spots" with low collagen density as well as areas of very high collagen content. This suggests a non-uniform mechanical stiffness across the lamina that may account for increased axon damage observed in glaucoma patients. The inferior temporal region of the ONH in particular is marked by low collagen density, which corresponds with clinical observations identifying this region as being more susceptible to damage during the onset of glaucoma. Further application of this technique will help characterize the relationship of age, race and gender on the morphology of the LC., (Copyright 2009 Elsevier Inc. All rights reserved.) more...

Purpose: To evaluate selective laser trabeculoplasty (SLT) as a replacement for medical therapy in controlled open-angle glaucoma., Design: Prospective, non-randomized, interventional clinical trial., Methods: SLT was performed inferiorly in 66 eyes of 66 patients with medically controlled primary open-angle glaucoma (OAG) or exfoliation glaucoma, and no history of glaucoma surgery. The primary outcome was number of medications at 6 and 12 months while maintaining a pre-determined target intraocular pressure (IOP)., Results: The mean of the differences in medications from baseline was 2.0 (95% confidence interval = 1.8-2.3) at 6 months, and 1.5 (1.27-1.73) at 12 months (P < .0001). The group mean of medications was 2.8 +/- 1.1 at baseline, 0.7 +/- 0.9 at 6 months, and 1.5 +/- 0.9 at 12 months (P < .0001). Reduction in medications was attained in 64 of 66 eyes (97%) at 6 months, and 52 of 60 (87%) at 12 months., Conclusion: SLT enabled a reduction in medicine in controlled OAG over 12 months. more...

Raised intraocular pressure is a common and frequently serious complication of anterior uveitis. The milieu of inflammatory cells, the mediators they release, and the corticosteroid therapy used to treat the uveitis can participate in the pathogenesis of uveitic glaucoma. These factors alter the normal anatomic structure of the anterior chamber and angle, influencing aqueous production and outflow. These changes act to disrupt the homeostatic mechanisms of intraocular pressure control. Structural changes in the angle can be acute, such as in secondary angle closure with pupillary block glaucoma, or chronic, such as combined steroid-induced and secondary open angle glaucoma. Management of uveitic glaucoma may be difficult because of the numerous mechanisms involved in its pathogenesis. Diagnostic and therapeutic decisions are guided by careful delineation of the pathophysiology of each individual case. The goal of treatment is to minimize permanent structural alteration of aqueous outflow and to prevent damage to the optic nerve head. This article reviews the pathogenesis of uveitic glaucoma, with specific attention to etiology. Medical and surgical therapies are also discussed, with emphasis on the more recent developments in each category. more...

Purpose: We reviewed the course of intraocular pressure, visual acuity, and complications in patients with shallow anterior chambers or vitreous prolapse who underwent insertion of glaucoma drainage tubes through the pars plana (after a complete posterior vitrectomy)., Methods: Thirteen patients (13 eyes) with uncontrolled glaucoma associated with shallow anterior chamber or vitreous prolapse and aphakia or pseudophakia underwent pars plana Baerveldt tube insertion after vitrectomy., Results: In 11 eyes the intraocular pressure was less than or equal to 15 mm Hg at a minimum follow-up of one year; the other two eyes underwent additional glaucoma surgery. Two of the 11 eyes with controlled intraocular pressure had limitation of ocular motility postoperatively. No retinal complications had occurred in any of the 13 eyes., Conclusion: This technique of combined pars plana vitrectomy and pars plana insertion of a Baerveldt tube provides intraocular pressure control in eyes with shallow anterior chamber or vitreous prolapse and glaucoma associated with pseudophakia or aphakia. more...

Bilateral trabeculectomies were performed on four normal cynomolgus monkeys. Highly purified bovine skin collagen implants with either 1 mg of 5-fluorouracil or physiologic saline (one each per monkey by randomized, masked assignment) were sutured under the scleral flaps. The randomization code was not broken until all clinical and histopathologic observations had been completed. Six weeks postoperatively, the 5-fluorouracil-treated eyes had more deeply open internal trabeculectomy ostia than the control eyes; however, the intraocular pressures were indistinguishable, the filtering blebs were only minimally different, and half of each group had trace or mild anterior subcapsular lenticular changes. Histologically, a multinucleated foreign body giant cell reaction was evident in all of the collagen implants, but the 5-fluorouracil-treated eyes had less vigorous or delayed reactions compared to the control eyes. The collagen implant appears to be a poor drug delivery system in this model of glaucoma filtering surgery, because it incites a granulomatous inflammatory reaction. more...

Quantitative measurements of the composition of axonal bundles were made from electron micrographs for six levels within the intraocular portion of the optic nerve head of the rhesus moneky. The proportion of the areas occupied by axonal cytoplasm, glial cytoplasm, mitochondria, and myelin was calculated. Average axonal diameters were determined at each location. Axonal bundles acquired progressively more interaxonal glial tissue as they passed posteriorly from the region of the optic disk toward the optic nerve. Mitochondria were present within axons in increased numbers in the lamina choroidalis and lamina scleralis, and there may be focal expansions and constrictions of axons in the same regions. The overall cross-sectional area of the intraocular portion of the optic nerve expanded posterior to Bruch's membrane in part because of the addition of the interaxonal glial tissue. more...

Twenty patients with histopathologically confirmed sympathetic ophthalmia (Group 1) and eight patients with "presumed sympathetic ophthalmia," based on a clinical history of bilateral uveitis occurring within four months of a perforating ocular injury (Group 2), were typed for HLA-A, HLA-B, and HLA-C antigenic determinants by a micro-lymphocytotoxicity technique. HLA antigenic determinants found in Groups 1 and 2 were compared to a control group of 107 patients with sequelae of perforating ocular injuries from accidents, intraocular surgery, or corneal ulcers (Group 3). HLA-A11 antigen showed an increased frequency of 30% in Group 1 (relative risk = 11.0; P less than .002) and an increased frequency of 32% in Groups 1 + 2 (relative risk = 10.5; P less than .0005) compared to Group 3 (frequency = 4%). This finding was validated against a second control group of 453 healthy subjects without ocular disease or trauma (Group 4). This association suggests that a genetic factor may play an important role in the pathogenesis of sympathetic ophthalmia. more...

Cyclocryotherapy of the monkey eye reliably produces transient increased intraocular pressure followed by prolonged hypotony, during which papilledema occurs. Axoplasmic transport was studied while the intraocular pressure was both increased and decreased after cyclocryotherapy by autoradiography following the intravitreal injection of tritiated leucine and proline. Surgical fistulization of the anterior chamber was also used to produce hypotony and papilledema. Significant alterations of both the rapid and the slow components of axoplasmic transport were demonstrated in the nerve head during increased intraocular pressure, and in ocular hypotony with papilledema. more...

Cyclocryotherapy was a reliable method of producing prolonged decreased intraocular pressure and papilledema in the rhesus monkey. Histologic changes in papilledema caused by decreased pressure were indistinguishable from those in papilledema from increased intracranial pressure. Electron microscopic observations in papilledema after cyclocryotherapy suggested that the principal morphologic alteration in the optic disk is axonal swelling. Additionally, many mitochondria accumulated in some swollen axons. These changes, observed at the ultrastructural level, suggest that alternations of axoplasmic transport may play a significant role in the pathogenesis of swelling of the disk. more...

A 33-year-old woman with Hodgkin's disease developed a painless progressive loss of vision in both eyes. Despite an ophthalmoscopic appearance of white-yellow retinal necrosis and retinal hemorrhage similar to that described with Hodgkin's disease, no sign of the disorder was found at autopsy. Instead, widespread evidence of Herpesviridae family virus infection was present in several organs, including the retinas. Opportunistic infection, including herpes simplex and cytomegalovirus, should be considered when retinitis complicates Hodgkin's disease. more...

A 65-year-old woman had been observed for more than four years with bilateral chronic nongranulomatous uveitis and vitreous clouding of unknown cause. Her death was from reticulum cell sarcoma of the brain (microglioma). Both eyes were obtained post mortem. Histopathologic examination revealed malignant cell in the vitreous of both eyes, but no other tumor was demonstrable in the ocular tissues. Reticulum cell sarcoma should be suspected in middle-aged or older persons with chronic unilateral or bilateral uveitis of unknown cause who develop cerebral manifestations during the course of the disease. more...

We performed a clinical evaluation on a prototype version of the Tono-Pen hand-held tonometer. A masked, randomized design was used to compare the instrument with the Goldmann tonometer. We tested 270 eyes. For pressures of 6 to 24 mm Hg, the Tono-Pen tonometer measured, on average, 1.7 mm Hg higher than the Goldmann tonometer. This difference was statistically significant (P less than .0001). In the range above 24 mm Hg, no statistically significant difference was found in the pressures measured with the two instruments. Measurements made with the Tono-Pen were sufficiently close to those made with the Goldmann tonometer to be considered clinically accurate. more...

We studied the ultrastructural characteristics of an experimental model of traction retinal detachment secondary to a penetrating eye injury in the rhesus monkey. Cells with the characteristics of myofibroblasts were present in the intravitreal fibrous tissue and in epiretinal membranes. These cells were probably derived from many sources, and were capable of contraction through the mechanism of intracytoplasmic contractile proteins such as actin or myosin. The morphologic observations supported our hypothesis that traction retinal detachment is a cell-mediated event analogous to the processes of wound healing and wound contraction. The force of contraction is mediated by cell-to-cell and cell-to-vitreous connections and by glial bridges that connect epiretinal membranes to the retina. These ultrastructural studies, which provide insight into the pathogenesis of traction retinal detachment in the experimental animal model, may well have significant clinical relevance. more...

Cystinosis is a rare autosomal recessive metabolic disorder that results in the widespread accumulation of cystine crystals in ocular tissues as well as in bone marrow, liver, spleen, lymph nodes, and kidneys. We treated a case of pupillary-block glaucoma in a 19-year-old woman caused by cystine accumulation in the iris stroma. Trabeculectomy and iridectomy relieved the pupillary block and decreased the intraocular pressure. Histologic examination disclosed the presence of crystals in the conjunctival and iris stroma and in the iris pigment epithelium. Crystals were also found within conjunctival mast cell granules, confirming the lysosomal nature of cystinosis. more...

A systematic study of axoplasmic transport in the normal optic nerve head is essential to the understanding of the role of this process in the pathogenesis of disease of the optic nerve. Twenty-one eyes from normal adult rhesus monkeys were subjected to intravitreal injections of tritiated leucine (3H) or proline (3H). Light microscopic autoradiographs were prepared on these eyes and optic nerves six hours to 60 days after injection. The isotope that was incorporated in cytoplasmic components associated with the slow phase of axoplasmic transport (3H leucine) became concentrated in the temporal region of the optic nerve head, unevenly distributed within axons in the axonal bundles, and apparently accumulated in axons or glial cells, or both, in the lamina choroidalis and scleralis as a broad pulse of isotope moved across the optic nerve head. Several anatomic factors, including the distribution of macular fibers, increasing amounts of glial cells within the same axonal bundles as the optic nerve passed from the lamina retinalis to the lamina scleralis, and the abrupt addition of myelin sheaths to axons behind the lamina scleralis, contributed to the complex distribution of isotope in the normal optic nerve head. Glial cell labeling was especially prominent with 3H proline. more...