Aqueous shunts for glaucoma.

BACKGROUND: Aqueous shunts are employed for intraocular pressure (IOP) control in primary and secondary glaucomas that fail medical, laser, and other surgical therapies. OBJECTIVES: This review compares aqueous shunts for IOP control and safety. SEARCH STRATEGY: We searched CENTRAL, MEDLINE, PubMed, EMBASE, NRR all in January 2006, LILACS to February 2004 and reference lists of included trials. SELECTION CRITERIA: We included all randomized and quasi-randomized trials in which one arm of the study involved shunts. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data for included studies and a third adjudicated discrepancies. We contacted investigators for missing information. We used fixed-effect models and summarized continuous outcomes using mean differences. MAIN RESULTS: We included fifteen trials with a total of 1153 participants with mixed diagnoses. Five studies reported details sufficient to verify the method of randomization but only two had adequate allocation concealment. Data collection and follow-up times were variable.Meta-analysis of two trials comparing Ahmed implant with trabeculectomy found trabeculectomy resulted in lower mean IOPs 11 to 13 months later (mean difference 3.81 mm Hg, 95% CI 1.94 to 5.69 mm Hg). Meta-analysis of two trials comparing double-plate Molteno implant with the Schocket shunt was not done due to substantial heterogeneity. One study comparing ridged with standard double-plate Molteno implants found no clinically significant differences in outcome. Two trials investigating the effectiveness of adjunctive mitomycin (MMC) with the Molteno and Ahmed implants found no evidence of benefit with MMC. Two trials that investigated surgical technique variations with the Ahmed found no benefit with partial tube ligation or excision of Tenon's capsule. One study concluded there were outcome advantages with a double versus a single-plate Molteno implant and one trial comparing the 350 mm(2) and 500 mm(2) Baerveldt shunts found no clinically significant advantage of the larger device but neither of these trials included all patients randomized. One study suggested improved clinical outcome when MMC was employed with a newly described shunt including ultrasound supporting the conclusion. One small study did not demonstrate an outcome advantage to systemic steroid use postoperatively with single-plate Molteno shunts. One study comparing endocyclophotocoagulation (ECP) with Ahmed implant in complicated glaucomas found no evidence of better IOP control with Ahmed implant over ECP. AUTHORS' CONCLUSIONS: Relatively few randomized trials have been published on aqueous shunts and methodology and data quality among them is poor. To date there is no evidence of superiority of one shunt over another.

Changes in axial length following trabeculectomy and glaucoma drainage device surgery.

AIM: This study examines the changes in axial length (AL) after trabeculectomy and glaucoma drainage device (GDD) surgery and enabled an equation to be derived allowing prediction of AL change after filtering surgery. METHODS: This was a prospective, interventional case series from the Glaucoma Service of the Doheny Eye Institute. PATIENT POPULATION: One eye of 39 patients undergoing trabeculectomy and 22 undergoing Baerveldt tube shunt implantation for uncontrolled glaucoma. INTERVENTION: These patients had AL measurements by non-contact, partial coherence interferometry preoperatively, at 1 week, 1 month, and >3 months after surgery. MAIN OUTCOME MEASURES: Axial length and intraocular pressure were compared at preoperative and postoperative visits. Postoperative intraocular pressure (IOP) was categorised as hypotonous (0-4 mm Hg), low (5-9), normal (10-17), and high (18 or more). RESULTS: There was a statistically significant reduction in IOP after 3 months of -12.8 (SD 1.5) mm Hg following trabeculectomy (p<0.001), and -10.7 (1.9) mm Hg after GDD (p<0.001). There was a statistically significant reduction in AL, which was similar after trabeculectomy and GDD at all time points (p<0.001), of -0.15 (0.03) and -0.21 (0.04) mm (1 week), -0.18 (0.02) and -0.10 (0.02) mm (1 month), and -0.16 (0.03) and -0.15 (0.03) mm (3 months). At 3 months or later the AL reduction was related to postoperative IOP and to the amount of IOP reduction (p<0.05, stepwise multiple regression). 10.2% (4/39) of trabeculectomy patients had hypotony after 3 months, with a mean AL reduction (-0.39 (0.11)) that was statistically significantly lower (p<0.01) than the other trabeculectomy eyes (-0.14 (0.15)). CONCLUSIONS: There is a small but statistically significant decrease in AL after both trabeculectomy and GDD surgery, greater in eyes that are hypotonous after surgery. The authors suggest that AL reduction can be predicted after 3 months by the formula: AL reduction (mm) = -199+0.006 x IOP reduction+0.008 x final IOP.

Demonstration of bilateral projection of the central retina of the monkey with horseradish peroxidase neuronography.

In the primate, ganglion cells of the temporal retina project ipsilaterally and those of the nasal retina, contralaterally into the optic tract. The vertical meridian passing through the fovea defines the border between these two populations of ganglion cells and has been demonstrated in four Macaque monkeys after unilateral injection of horseradish peroxidase into the dorsal lateral geniculate nucleus and examination of the pattern of retrograde labeling of those ganglion cells projecting to the injected side. A median 1 degree vertical strip in which ipsi- and contralaterally projecting ganglion cells intermingle was found, confirming the report by Stone et al. ('73). In addition, occasional extrafoveal labeled ganglion cells were found as far as 2 degrees from the vertical midline in the otherwise unlabeled hemiretinae. These ganglion cells were not numerous and had somata of all sizes, suggesting that they do not constitute a separate class of ganglion cells as found in the temporal retina of the cat. In contrast to the description by Stone et al. ('73), the strip of vertical overlap did not show a constant width through the fovea, since mixing of labeled and unlabeled ganglion cells was found in a band approximately 1/2 degree wide along both the nasal and temporal rims of the foveal pit which is 500 mum (2 degrees) in diameter. Beyond these 1/2 degree arcs, the appropriate hemiretina was either completely unlabeled, or contained virtually every ganglion cell labeled on the side projecting to the injected dorsal lateral geniculate nucleus. The scattered labeled ganglion cells rimming an otherwise unlabeled hemifovea represent a possible anatomical basis for the phenomenon of "macular" or "foveal sparing" in which unilateral damage to the occipital cortex produces homonymous hemianopsia with sparing of a small island of centralmost vision extending about 1 degree from the foveal center. From this study, it is not possible to define the receptive fields or specific photoreceptor connections of the ganglion cells labeled with horseradish peroxidase, so that at the present time quantitative correlations cannot be made between the numbers of ganglion cells remaining on the affected side of the fovea and the extent of preservation of visual function in the spared zone. The presence of labeled ganglion cells rimming the fovea in its entirety is compatible with the sequence of foveal development in late prenatal life. After lateral displacement both nasally and temporally of ganglion cells which initially lay in the median vertical overlap strip of 1 degree, in the adult retina a strip approximately 1/2 degree wide around the perimeter of the foveola should contain a mixture of ipsi- and contralaterally projecting ganglion cells. The total population of ganglion cells beyond this 1/2 degree band should be completely ipsi- or contralateral in their projection patterns, as is observed...

Displaced ganglion cells in the retina of the monkey.

Horseradish peroxidase has been injected into the dorsal lateral geniculate nucleus of macaque monkeys to label ganglion cells of the retina by retrograde axoplasmic transport. Displaced ganglion cells, with somata in the inner nuclear layer and dendrites in the inner plexiform layer, were detected by virtue of their filling with peroxidase-positive granules. These cells were numerous in the peripapillary region, but relatively uncommon elsewhere in the retina.

Orthograde and retrograde axoplasmic transport during acute ocular hypertension in the monkey.

Orthograde and retrograde axoplasmic transport have been studied in the optic nerve heads of 37 Macaca fascicularis eyes with normal or elevated intraocular pressure (IOP) produced by cannulation of the anterior chamber. Orthograde transport was labeled by 3H-amino acids injected intravitreally and incorporated into retinal ganglion cell proteins. Retrograde transport was studied in the same eyes by injecting horseradish peroxidase (HRP) into one or both optic tracts and dorsal lateral geniculate nuclei (dLGN). Both tracers accumulated in the lamina scleralis (LS) of eyes maintained at pressures of 25 to 150 mm. Hg for 12 to 28 hours (pressure in normal controls = 10 to 14 mm. Hg) but the HRP technique was markedly more sensitive. The degree of retrograde transport obstruction in the LS appeared to be directly proportional to both the height and the duration of elevated IOP. In one experiment, the blockades of orthograde and retrograde transport induced at 50 mm. Hg were demonstrated to be reversible. Serial reconstructions of radioautographs and peroxidase-reacted sections of the optic nerve heads demonstrated that the orthograde and retrograde transport obstructions were coincidental anatomically by light microscopy in the LS and occurred most prominently in the temporal quadrants of the nerve head. These transport obstructions occurred at moderate elevations of IOP (25 TO 50 mm. Hg) despite (1) elevated arterial PO2 levels during inhalation of 100 percent oxygen and (2) intact nerve head capillary circulation, as demonstrated by perfusion with nucleated avian erythrocytes.

Intraocular pressure in Lewis rats.

PURPOSE: To perform noninvasive measurements of intraocular pressure (IOP) in rats, the Tono-Pen-1 and Tono-Pen-2 were calibrated against direct manometry. Normal values and the long-term fluctuations of IOP in Lewis rats were established. METHODS: For calibration, 24 eyes were cannulated and connected to a pressure transducer with a chart recorder. IOP was increased from 5 to 40 mm Hg in 5 mm Hg increments, and from 40 to 60 mm Hg in 10 mm Hg increments. After each incremental increase, IOP was measured with a Tono-Pen-1 and a Tono-Pen-2 tonometer. To determine normal IOP in Lewis rats, IOP was measured with a Tono-Pen-1 in 229 eyes of 115 rats, and a histogram of normal IOP was established. To ascertain long-term IOP fluctuations, the pressure in 52 eyes of 26 rats was measured every day between 8:30 and 9:30 AM for 7 consecutive days. RESULTS: Plotting the mean Tono-Pen readings for each eye against the transducer IOP produced two regression formulas: y = 1.819 + 0.711 x (r2 = 0.92) for Tono-Pen-1, and y = -1.291 + 0.784 x (r2 = 0.97) for Tono-Pen-2. The normal IOP in rats was 17.30 +/- 5.25 mm Hg (90% confidence interval: 7.28 and 26.98 mm Hg for the lower and upper limits of normal IOP). There was no long-term fluctuation in IOP (P = 0.55). CONCLUSIONS: IOP can be measured accurately in living rats with the Tono-Pen-1 or the Tono-Pen-2.

The organization of nerve fiber bundles in the primate optic nerve head.

Horseradish peroxidase was injected into various areas of the optic disc of monkeys to label retrograde axoplasmic transport and permit identification and mapping of ganglion cells projecting through the areas of injection. Peripheral ganglion cell axons project through the deeper layers of the peripapillary nerve fiber layer (NFL) and enter the peripheral optic nerve. Peripapillary ganglion cell axons project through those coming from peripheral locations to superficial positions in the NFL, then to the central optic nerve. The Bjerrum portion of the optic nerve head includes approximately the central 30 degrees of the superior and inferior temporal quadrants of the disc. The course of nerve fiber bundles corresponding to those most susceptible to glaucoma (Bjerrum area) is regularly and predictably organized horizontally and vertically in the nerve head.

Cataract extraction in the sympathizing eye.

Cataract extraction was performed on the sympathizing eyes of six patients with sympathetic ophthalmia. In five patients the clinical diagnosis of sympathetic ophthalmia was supported by the results of histologic examination of the exciting eye. The postoperative period averaged 12 years, and visual acuities ranged from 20/25 to light perception. The presence of posterior synechiae posed the major complicating operative factor. Cystoid macular edema, vitreous opacity, pupillary membrane formation, and corneal opacification were associated with postoperative visual impairment in four cases. We conclude that the underlying status of the sympathizing eye at the time of cataract extraction and postoperative management are critical factors that influence ultimate visual outcome.

Foveal sparing. New anatomical evidence for bilateral representation of the central retina.

The pattern of retinal ganglion cell projections to the dorsal lateral geniculate nuclei has been demonstrated with horseradish peroxidase neuronography. A 1 degree-wide strip centered on the vertical meridian has been found in which ipsilaterally and contralaterally projecting ganglion cells intermingle. This strip expands to a width of 3 degrees at the fovea, since mixing of horseradish peroxidase-labeled and unlabeled ganglion cells was found in a band approximately 0.5 degrees wide along both the nasal and temporal rims of the foveola. These labeled ganglion cells rimming the foveal pit in its entirety represent a possible anatomical basis for "foveal sparing".

Axoplasmic transport in ocular hypotony and papilledema in the monkey.

Orthograde and retrograde axoplasmic transport were studied in optic nerve heads of seven hypotensive Macaca fascicularis eyes. Orthograde transport was studied by radioautography after intravitreal radioisotope injections. Retrograde transport was studied in the same eyes by horseradish peroxidase injection into the dorsal lateral geniculate nuclei or optic tracts. Three eyes had developed marked papilledema before injections. Orthograde axoplasmic transport was blocked in swollen axons of the optic disc anterior to Bruch membrane and in the lamina scleralis. Retrograde transport was blocked in axons within the lamina scleralis along the posterior edges of transverse scleral beams and in axons in the choroidal portion of the nerve head posterior to Bruch membrane. These results support the general concept that axoplasmic transport in the optic nerve head is sensitive to alterations in intraocular pressure, either increases or decreases. The edges of Bruch membrane and the openings in the lamina scleralis may constrict axon bundles in ocular hypotony.

Ultrasound in early thyroid orbitopathy.

Fourteen patients with unilateral exophthalmos were found on A-scan ultrasound examination to have enlarged extraocular muscles. Thyroid dysfunction later was documented in 12 patients (86%) by laboratory tests and subsequent clinical examination. The suspicion of endocrine orbitopathy was based on the presence of enlarged extraocular muscles in both orbits and on the difference in thickness between corresponding muscles. A-scan orbital examination including specific muscle measurements is a simple and apparently reliable method of diagnosing early thyroid orbitopathy.

Epithelial ingrowth.

A 74-year-old woman had a radical anterior segment resection for epithelial ingrowth following cataract extraction. Light microscopy demonstrated the presence of a sheet of cells morphologically similar to conjunctival epithelium covering the superior half of the inner surface of the cornea, iris, and ciliary processes. Electron microscopy revealed that frequent hemidesmosomes and a well-developed basal lamina were consistently present along the base of the ingrowing epithelium. The tissue immediately beneath the ingrowing epithelium, lining the cornea, trabecular meshwork and iris, morphologically resembled the subepithelial zone that has been described along the human skin epidermal-dermal junction. Additionally, focal areas of necrosis were noted in the trabecular meshwork. The major structural alterations induced on the surfaces of intraocular structures by the invading epithelium and the associated necrosis probably are responsible for the glaucoma which occurs with epithelial ingrowth.

Pseudorheumatoid nodule involving the orbit.

We report a clinicopathologic study of an unusual case of pseudorheumatoid nodule involving the right orbit of a child. Pathologically, the orbital lesion was similar to subcutanous nodules of rheumatoid arthritis and rheumatic fever. The physical findings and laboratory studies in our case did not reveal any evidence of systemic disease. Based on a review of reported cases involving other locations, this lesion appears clinically benign in children.

Prognosis in uveal melanoma with extrascleral extension.

Two thirds of 60 patients followed up after enucleation for uveal melanoma with extrascleral extension eventually died of metastatic disease. Large intraocular tumor size, more malignant cell types, optic nerve invasion, and surgical transection or nonencapsulation of the extraocular tumor margin were found to be significantly correlated with development of metastases. Advanced age at enucleation and large intraocular tumor size were significantly associated with early metastatic death. Recurrence of tumor in the orbit was identified in 10% of the patients and was significantly correlated with large intraocular tumor size and optic nerve invasion. Early exenteration, performed in seven cases, did not improve prognosis. Application of Bayesian methods produced a multifactorial model for prediction of metastatic disease within 13 years after enucleation.

Experimental inflammatory serous detachment of the retina.

Rhesus monkey eyes were studied after the development of inflammatory serous retinal detachments following internal carotid artery injection of live, yeast-phase Histoplasma capsulatum organisms. Horseradish peroxidase (HRP) was used as a tracer to examine the inner and outer blood-retinal barriers. The HRP was present in a decreasing gradient from the choroid into the subretinal space and was not found to have leaked from retinal vessels. The source of subretinal fluid in this model of inflammatory serous retinal detachment was leakage from the choroid through a defective outer blood-retinal barrier, induced by disruption of the retinal pigment epithelium. This model has relevance to understanding the serous retinal detachments common to diseases affecting the choroid.

Herpesvirus hominis encephalitis and retinitis.

A previously healthy 44-year-old man died three weeks after the simultaneous onset of encephalitis and retinitis. Fundus changes were bilateral and included papillitis, rapidly progressive central retinal vein obstruction, and massive exudative retinal detachment. A 16-fold rise in herpesvirus hominis antibodies occured between the 10th and 20th days of illness. At autopsy, the brain showed changes characteristic of herpetic encephalitis, and cultures of the brain yielded Herpesvirus hominis type I. Intranuclear inclusion bodies typical of those produced by Herpesvirus were found by light microscopy in brain, optic nerves, retina, and choroid. Herpesvirus particles were found by electron microscopy in brain, optic nerve, and retina.

Time parameters for glaucoma procedures.

Changes in physician reimbursement and the practice environment have emphasized the importance of determining physician time for procedures and services. Forty-five percent of the members of the American Glaucoma Society responded to a mail survey of estimates of the length of time and number of visits for the preoperative, operative, and 90-day postoperative care for six common glaucoma procedures. Results suggest a significant underestimation of time for trabeculectomies exists in the original and new resource-based relative value scale work values. Further, 47% to 53% of surgeons hospitalize patients on at least the first postoperative day. There were no apparent time efficiencies between "high-" and "low-volume" respondents. Thus, careful attention should be paid to the accuracy of certain time estimates and the resulting work values in the resource-based relative value scale. Additional work in this and other areas may prove illuminating.

Penetrating keratoplasty: changing indications, 1947 to 1978.

Corneal buttons submitted to the Estelle Doheny Eye Foundation from 1947 through 1978 were studied. According to a study of 710 corneal specimens processed during 31 years, the leading indications for penetrating keratoplasty were aphakic bullous keratopathy, regrafts, keratoconus, and Fuchs' endothelial dystrophy. Intraocular lenses were associated with 22% of all specimens of aphakic bullous keratopathy in 1974, increasing to 68% of all aphakic bullous keratopathy corneas in 1978. Histopathologic appearance of aphakic bullous keratopathy corneas with or without an intraocular lens was similar.

Ocular findings in thoracic-pelvic-phalangeal dystrophy.

Two unrelated patients with thoracic-pelvic-phalangeal dystrophy syndrome had retinal degeneration. A pathologic study of both eyes from one of the patients showed severe degeneration of the peripheral retina, with predominantly cone-type cells remaining.

Glaucoma associated with uveitis.

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.