Nailfold capillary morphology in exfoliation syndrome.

PurposeThe purpose of the study was to investigate nailfold microvascular morphology in exfoliation syndrome with or without glaucoma (XFS/XFG) compared with primary open-angle glaucoma (POAG) and control subjects using nailfold capillary videomicroscopy.Patients and methodsWe used a JH-1004 capillaroscope to perform nailfold capillary videomicroscopy on the fourth and fifth digit of the non-dominant hand. We enrolled 56 XFS/XFG patients, 87 POAG patients, and 75 control subjects. Masked observers graded the videos for hemorrhages, avascular zones ≥200 microns (µm), and degree of microvascular tortuosity on a four-point subjective scale. Multivariable odds ratios, 95% confidence intervals and P-for trends for assessing the relation between morphological changes and POAG or XFS/XFG were obtained from logistic regression analyses. We also assessed this relation with XFS/XFG compared with POAG in multivariable models.ResultsAfter adjusting for multiple covariates, nailfold hemorrhages, avascular zones ≥200 µm, and higher degree of vascular tortuosity were more common in XFS/XFG vs controls (P-for trend ≤0.0001) and in POAG vs controls (P-for trend ≤0.01). For each 100 capillaries, the number of hemorrhages was similar (P-for trend=0.91) between XFS/XFG and POAG patients; however, there were more avascular zones per 100 capillaries with borderline significance (P-for trend=0.04) in the XFS/XFG group. XFS/XFG patients had more tortuosity than POAG patients; specifically, having a tortuosity score ≥1.5 was associated with a 4.4-fold increased odds of XFS/XFG (95% confidence interval: 1.5-13.3) relative to a tortuosity score <1.0 (P-for trend=0.005).ConclusionA high degree of nailfold capillary tortuosity is a distinct non-ocular feature associated with XFS/XFG compared with either POAG or controls.

Increased post-traumatic survival of neurons in IL-6-knockout mice on a background of EAE susceptibility.

Axonal injury initiates a process of neuronal degeneration, with resulting death of neuronal cell bodies. We show here that in C57BL/6J mice, previously shown to have a limited ability to manifest a post-traumatic protective immunity, the rate of neuronal survival is increased if IL-6 is deficient during the first 24 hours after optic nerve injury. Immunocytochemical staining preformed 7 days after the injury revealed an increased number of activated microglia in the IL-6-deficient mice compared to the wild-type mice. In addition, IL-6-deficient mice showed an increased resistance to glutamate toxicity. These findings suggest that the presence of IL-6 during the early post-traumatic phase, at least in mice that are susceptible to autoimmune disease development, has a negative effect on neuronal survival. This further substantiates the contention that whether immune-derived factors are beneficial or harmful for nerve recovery after injury depends on the phenotype of the immune cells and the timing and nature of their dialog with the damaged neural tissue.

Optic nerve transection in monkeys may result in secondary degeneration of retinal ganglion cells.

PURPOSE: Interest in neuroprotection for optic neuropathies is, in part, based on the assumption that retinal ganglion cells (RGCs) die, not only as a result of direct (primary) injury, but also indirectly as a result of negative effects from neighboring dying RGCs (secondary degeneration). This experiment was designed to test whether secondary RGC degeneration occurs after orbital optic nerve injury in monkeys. METHODS: The superior one third of the orbital optic nerve on one side was transected in eight cynomolgus monkeys (Macaca fascicularis). Twelve weeks after the partial transection, the number of RGC bodies in the superior and inferior halves of the retina of the experimental and control eyes and the number and diameter of axons in the optic nerve were compared by detailed histomorphometry. Vitreous was obtained for amino acid analysis. A sham operation was performed in three additional monkeys. RESULTS: Transection caused loss of 55% +/- 13% of RGC bodies in the superior retina of experimental compared with fellow control eyes (mean +/- SD, t-test, P < 0.00,001, n = 7). Inferior RGCs, not directly injured by transection, decreased by 22% +/- 10% (P = 0.002). The loss of superior optic nerve axons was 83% +/- 12% (mean +/- SD, t-test, P = 0.0008, n = 5) whereas, the inferior loss was 34% +/- 20% (P = 0.02, n = 5). Intravitreal levels of glutamate and other amino acids in eyes with transected nerves were not different from levels in control eyes 12 weeks after injury. Fundus examination, fluorescein angiography, and histologic evaluation confirmed that there was no vascular compromise to retinal tissues by the transection procedure. CONCLUSIONS: This experiment suggests that primary RGC death due to optic nerve injury is associated with secondary death of surrounding RGCs that are not directly injured.

Vaccination for neuroprotection in the mouse optic nerve: implications for optic neuropathies.

T-cell autoimmunity to myelin basic protein was recently shown to be neuroprotective in injured rat optic nerves. In the present study, using the mouse optic nerve, we examined whether active immunization rather than passive transfer of T-cells can be beneficial in protecting retinal ganglion cells (RGCs) from post-traumatic death. Before severe crush injury of the optic nerve, SJL/J and C3H.SW mice were actively immunized with encephalitogenic or nonencephalitogenic peptides of proteolipid protein (PLP) or myelin oligodendrocyte glycoprotein (MOG), respectively. At different times after the injury, the numbers of surviving RGCs in both strains immunized with the nonencephalitogenic peptides pPLP 190-209 or pMOG 1-22 were significantly higher than in injured controls treated with the non-self-antigen ovalbumin or with a peptide derived from beta-amyloid, a non-myelin-associated protein. Immunization with the encephalitogenic myelin peptide pPLP 139-151 was beneficial only when the disease it induced, experimental autoimmune encephalomyelitis, was mild. The results of this study show that survival of RGCs after axonal injury can be enhanced by vaccination with an appropriate self-antigen. Furthermore, the use of nonencephalitogenic myelin peptides for immunization apparently allows neuroprotection without incurring the risk of an autoimmune disease. Application of these findings might lead to a promising new approach for treating optic neuropathies such as glaucoma.

RGC death in mice after optic nerve crush injury: oxidative stress and neuroprotection.

PURPOSE: To establish a method for morphometric analysis of retrogradely labeled retinal ganglion cells (RGCs) of the mouse retina, to be used for the study of molecular aspects of RGC survival and neuroprotection in this model; to evaluate the effect of overexpression of Cu-Zn-superoxide dismutase (CuZnSOD) on RGC survival after severe crush injury to the optic nerve, and to assess the effect of the alpha2-adrenoreceptor agonist brimonidine, recently shown to be neuroprotective, on RGC survival. METHODS: A severe crush injury was inflicted unilaterally in the orbital portion of the optic nerves of wild-type and transgenic (Tg-SOD) mice expressing three to four times more human CuZnSOD than the wild type. In each mouse all RGCs were labeled 72 hours before crush injury by stereotactic injection of the neurotracer dye FluoroGold (Fluorochrome, Denver, CO) into the superior colliculus. Survival of RGCs was then assessed morphometrically, with and without systemic injection of brimonidine. RESULTS: Two weeks after crush injury, the number of surviving RGCs was significantly lower in the Tg-SOD mice (596.6 +/- 71.9 cells/mm(2)) than in the wild-type control mice (863. 5 +/- 68 cells/mm(2)). There was no difference between the numbers of surviving RGCs in the uninjured retinas of the two strains (3708 +/- 231.3 cells/mm(2) and 3904 +/- 120 cells/mm(2), respectively). Systemic injections of brimonidine significantly reduced cell death in the Tg-SOD mice, but not in the wild type. CONCLUSIONS: Overexpression of CuZnSOD accelerates RGC death after optic nerve injury in mice. Activation of the alpha2-adrenoreceptor pathway by brimonidine enhances survival of RGCs in an in vivo transgenic model of excessive oxidative stress.

Pneumatic retinopexy as supplemental therapy for persistent retinal detachment after scleral buckling operation.

PURPOSE: Persistent retinal detachment following scleral buckling may be caused by persistent open retinal tears with a large amount of subretinal fluid, despite proper positioning of the buckle. In this study we evaluated the effectiveness of supplemental pneumatic retinopexy in flattening of the detached retina. METHODS: During 1990-1994 twelve cases of persistent retinal detachment following scleral buckling operation with appropriate position of the buckle, underwent supplemental gas injection. RESULTS: Reattachment of the retina with complete absorption of the subretinal fluid was observed within 24-48 hours from the gas injection in all eyes. Three eyes redetached and required additional operations. At the end of the follow-up (mean 16 months) the retina was attached in all eyes, and the visual acuity was 20/120 or better in 11 eyes, and 20/30 or better in 7 eyes. No complications were observed. CONCLUSION: Pneumatic retinopexy for persistent retinal detachment, following scleral buckling, is effective in obtaining fast flattening of the retina and achieving good visual results.

Confocal tomographic angiography of the optic nerve head in patients with glaucoma.

PURPOSE: To demonstrate the superficial and deep blood supply of the optic nerve using a new method, confocal tomographic angiography, which combines two new techniques, confocal laser scanning ophthalmoscopy and indocyanine green angiography, into one system. METHODS: In a prospective study using confocal tomographic angiography, we evaluated the correlation between the vascular supply of the optic nerve and that of the visual field in 90 eyes of 49 subjects (25 eyes of 20 subjects with normal visual field and 65 glaucomatous eyes of 39 subjects with visual field defects; 10 subjects each had one eye with normal visual field and one with visual field defects). RESULTS: In 22 of 25 eyes with a normal visual field, a diffuse microvascular filling pattern of the optic disk area was apparent with no filling defects. The confocal tomographic angiography of 49 of 65 glaucomatous eyes had good correlation with their visual field defect location. In 20 of 27 eyes with superior visual field loss, an inferior vascular filling defect was detected. In 10 of 13 eyes with inferior visual field loss, a superior vascular filling defect was detected. In 10 of 15 eyes with superior and inferior visual field loss, inferior and superior vascular filling defects were detected. Finally, in nine of 10 eyes with total visual field loss, no vascularity of the optic disk could be detected. CONCLUSION: Confocal tomographic angiography is a new imaging technology that may be applied for the evaluation of the vascular supply of the optic nerve head.

Fornix-based trabeculectomy with mitomycin-C.

BACKGROUND AND OBJECTIVE: Mitomycin-C (MMC) has been shown to improve the surgical success of trabeculectomy; however, the advantages of MMC have been evaluated almost entirely as an adjunct to limbal-based trabeculectomy. This study evaluated the efficacy and safety of fornix-based trabeculectomy with MMC for glaucomatous patients. PATIENTS AND METHODS: Between January 1993 and April 1995, 71 patients underwent fornix-based trabeculectomy with topical application of 0.4 mg/ml of MMC for 3 minutes. The conjunctiva-Tenon's capsule flap was spread over the limbus and sutured in order to create a visible crease with a water-tight closure. The mean follow-up time was 14.5 months. RESULTS: The mean intraocular pressure (IOP) before surgery was 32.4 +/- 9.7 mm Hg. The average postoperative IOP was 14.04 +/- 9.57 mm Hg. An IOP of 20 mm Hg or less was observed in 57 eyes (80%). Postoperatively, 37 eyes (52%) required no additional medical therapy. One month after surgery, only 2 patients had wound leakage with hypotony and choroidal detachment. Two eyes (3%) had suprachoroidal hemorrhage with loss of vision. A conjunctival "buttonhole" occurred in 2 eyes (3%), but only 1 persisted more than a month. CONCLUSIONS: Fornix-based trabeculectomy using intraoperative application of 0.4 mg/ml of MMC for 3 minutes was found to be as safe and effective as limbal-based trabeculectomy with MMC.

Laser scanning tomography and angiography of the optic nerve head for the diagnosis and follow-up of glaucoma.

New imaging technologies allow us to detect and follow very subtle changes of the structure and perfusion of the optic nerve head. Two of these technologies, confocal scanning laser ophthalmoscopy and confocal tomographic angiography are reviewed, focusing on new data and advances reported in the past year. These and other technologies (eg, nerve fiber layer polarimetry, optical coherent topography, and laser doppler flowmetry) will enhance the ability to diagnose and monitor glaucomatous disc damage.