Inhibition of posterior capsule opacification with an immunotoxin specific for lens epithelial cells: 24 month clinical results.

PURPOSE: To assess the safety and effectiveness of an immunotoxin, MDX-RA, designed to inhibit posterior capsule opacification (PCO). SETTING: Eleven private practices in the United States. METHODS: This study comprised 63 eyes of 63 patients having extracapsular cataract extraction by phacoemulsification; these patients were enrolled in a Phase I/II clinical investigation of the immunotoxin MDX-RA. At the close of surgery, 21 patients were treated with placebo, 23 patients with 50 units of the immunotoxin, and 19 patients with 175 units of the immunotoxin as an aqueous solution. The patients were monitored for 24 months after primary cataract surgery using external eye and slitlamp examinations, visual acuity assessment, ophthalmoscopy, pachymetry, tonometry, endothelial cell counts, and lens capsule photography. Posterior capsule opacification, recorded on lens capsule photographs, was graded independently by a committee of 3 cataract surgeons. The incidence of neodymium:YAG (Nd:YAG) capsulotomy was projected from the opacification results. RESULTS: The immunotoxin, at the 50 unit dose, was well tolerated and effective in inhibiting PCO. At the 175 unit dose, there was a trend toward increased postoperative inflammation that was transient with no residua. From 6 to 24 months postoperatively, the 50 unit dose significantly inhibited PCO compared with the placebo (P < .05). This significant reduction in PCO translated into a significantly lower projected need for Nd:YAG capsulotomy in the 50 unit than the placebo group (P < .004). About 60% in the placebo group and 4% in the 50 unit group were projected to need an Nd:YAG capsulotomy by 3 years postoperatively. CONCLUSION: The immunotoxin was well tolerated and was effective in reducing PCO for up to 24 months after cataract surgery. Although these preliminary results are encouraging, a larger study is underway to determine whether the reduction in PCO by the immunotoxin decreases the need for Nd:YAG capsulotomy.

Mathematical model to predict the need for neodymium: YAG capsulotomy based on posterior capsule opacification rate.

PURPOSE: To evaluate a model to project the estimated time required before patients having primary phacoemulsification require neodymium:YAG (Nd:YAG) laser capsulotomy. SETTING: Eleven private practices in the United States. METHODS: Projections of time to capsulotomy were based on assessment of the early development of posterior capsule opacification (PCO) over time. The PCO data were collected during a clinical study to evaluate MDX-RA, an investigational immunotoxin designed to limit epithelial cell growth, preventing postsurgical PCO. From the PCO data, the estimated time to Nd:YAG capsulotomy in a placebo-treated group was compared with the actual time to capsulotomy in a cohort of patients from general practice who had had phacoemulsification. RESULTS: By 6 months, the mean Opacification Index in the MDX-RA group was significantly lower than that in the placebo group (P < .05) and it remained significantly lower at 12 (P < .001), 18 (P < .001), and 24 (P < .016) months. The rate of PCO in the MDX-RA group was approximately 6 times lower than that in the placebo group (P < .0004). Fifty-seven percent in the placebo group and 4% in the MDX-RA group were projected to require an Nd:YAG capsulotomy within 3 years of primary cataract surgery. Projected values for the placebo group were similar to actual values observed in the population-based cohort. CONCLUSIONS: This technique could be used to predict the need for Nd:YAG capsulotomy using early measurements of PCO.

Inhibition of cell proliferation on lens capsules by 4197X-ricin A immunoconjugate.

PURPOSE: To evaluate the cytotoxicity of immunotoxin 4197X-ricin A (4197X-RA) and its ability to inhibit protein synthesis and human lens epithelial cell (LEC) proliferation on the inner surface of the lens capsule. SETTING: Houston Biotechnology, Inc., The Woodlands, Texas. METHODS: A cell culture system was established using human LECs as a model for the proliferation of remnant LECs that occurs during posterior capsule opacification (PCO) after extracapsular cataract extraction. The LEC culture system was also used in vitro for testing compounds that might inhibit this process in vivo. Human LECs were cultured on the surface of the original lens capsule fixed to collagen. Variability was reduced by dissecting each lens capsule into equivalent halves and exposing the segments to immunotoxin 4197X-RA. RESULTS: Protein synthesis and LEC proliferation were almost completely inhibited at relatively low 4197X-RA concentrations after short exposure. The inhibitory effects persisted up to 3 weeks after withdrawal of the immunotoxin and after several media exchanges. CONCLUSION: Immunotoxin 4197X-RA may help prevent PCO after primary cataract surgery.

Traumatic brain injury, hemorrhagic shock, and fluid resuscitation: effects on intracranial pressure and brain compliance.

Intracranial hypertension following traumatic brain injury is associated with considerable morbidity and mortality. Hemorrhagic hypovolemia commonly coexists with head injury in this population of patients. Therapy directed at correcting hypovolemic shock includes vigorous volume expansion with crystalloid solutions. It is hypothesized that, following traumatic brain injury, cerebrovascular dysfunction results in rapid loss of brain compliance, resulting in increased sensitivity to cerebrovascular venous pressure. Increased central venous pressure (CVP) occurring with vigorous crystalloid resuscitation may therefore contribute to the loss of brain compliance and the development of intracranial hypertension. The authors tested this hypothesis in miniature swine subjected to traumatic brain injury, hemorrhage, and resuscitation. Elevated CVP following resuscitation from hemorrhage to a high CVP significantly worsened intracranial hypertension in animals with concurrent traumatic brain injury, as compared to animals subjected to traumatic brain injury alone (mean +/- standard error of the mean: 33.0 +/- 2.0 vs. 20.0 +/- 2.0 mm Hg, p < 0.05) or to animals subjected to the combination of traumatic brain injury, hemorrhage, and resuscitation to a low CVP (33.0 +/- 2.0 vs. 24.0 +/- 2.0 mm Hg, p < 0.05). These data support the hypothesis that reduction in brain compliance can occur secondary to elevation of CVP following resuscitation from hemorrhagic shock. This may worsen intracranial hypertension in patients with traumatic brain injury and hemorrhagic shock.

Refractive complications of cataract surgery after radial keratotomy.

Four patients underwent cataract extraction with posterior chamber lens implantation several years after radial keratotomy. All four patients experienced an initial hyperopic shift caused by an early postoperative corneal flattening of greater than or equal to 1 diopter. This flattening partially regressed, leaving the patients with a mean of 0.42 diopter of persistent corneal flattening. We found the Binkhorst and the Holladay intraocular lens calculation formulas to be more accurate than the SRK II for these patients. Corneal curvature measured with the keratometer was less accurate for intraocular lens calculations than was a value derived by subtracting the refractive change induced by the radial keratotomy from the patients' keratometric measurements obtained before radial keratotomy.

Complications of implanting three-piece C-loop posterior chamber lenses in the anterior chamber.

We have examined a total of four eyes in three patients who had undergone implantation of three-piece C-loop posterior chamber intraocular lenses into the anterior chamber. All four eyes exhibited four or more of the following complications: 1) loop encapsulation by peripheral anterior synechiae; 2) recurrent iritis; 3) central loop displacement with corneal endothelial touch; 4) progressive endothelial cell loss and corneal edema; 5) glaucoma; and 6) cystoid macular edema. Intraocular lens removal was required in all four eyes, and penetrating keratoplasty was performed in one. We believe that these complications are attributable to the inherent fallacies of fixating three-piece open-loop lenses in the anterior chamber angle.

Secondary intraocular lens implantation.

We conducted a retrospective study of our first 75 consecutive patients receiving secondary intraocular lens implants. Ninety-seven percent had postoperative visual acuities of greater than or equal to 20/40; 86%, greater than or equal to 20/25. Four percent of patients lost two or more lines of vision. Complications included retinal detachment (4%), transient cystoid macular edema (3%), transient corneal edema (3%), pupillary block glaucoma (1%), and progression of an epiretinal membrane (1%). Patients requiring anterior vitrectomy had the least favorable outcome, with a 28% incidence of retinal complications. Overall, these data show secondary intraocular lens implantations to be safe and effective. However, greater caution is recommended for patients who will require anterior vitrectomy because of the higher rate of retinal complications.

Glare following posterior chamber intraocular lens implantation.

We performed glare tests on patients following uncomplicated extracapsular cataract extraction and posterior chamber intraocular lens implantation and on noncataractous phakic patients. Three types of lenses were implanted to compare the effect of optic asphericity and ultraviolet filtration on glare. Glare testing was performed using the Miller-Nadler Glare Tester and Baylor Visual Function Tester. The glare scores of the pseudophakic and phakic patients were statistically similar. In the pseudophakic patients, factors associated with decreased glare performance were posterior capsular opacification and increased pupil size; the intraocular lens type did not significantly affect glare scores.

The effect of inhibition of angiogenesis in granulation tissue on wound healing and the fibroblast.

Protamine sulfate given in high doses can inhibit angiogenesis in the granulation tissue generated in an open wound. This is reflected by changes consistent with delayed vascular maturation in the morphology of the regenerating vessels seen at the gross, microscopic, and ultrastructural levels. A coincidental delay in wound healing as evidenced by impaired wound contraction occurs, although fibroblast duplication and myofibroblast differentiation appear intact. However, the fibroblasts contain little endoplasmic reticulum, the site of synthetic activity, and the surrounding collagen appears loose and disorganized. To unite these observations into a coherent pattern, we review the proposal that the endothelial cell, the fibroblast, and the extracellular stroma are interdependent and that maturation of each is necessary to maintain the momentum of wound healing. Our findings fit this mechanistic hypothesis but do not prove it. The abnormal vasoformation that may be initiated by protamine's anticoagulant properties could set the stage for impaired fibroblast synthetic activity. If collagenous stroma is deficient, both endothelial maturation and wound contraction wound fail. Although we saw these final events, to prove a series of cause and effect changes would require further study of the oxygen tension and the fibrin and collagen levels in granulation tissue.

Flexible anterior chamber intraocular lens expulsion.

We report a case of presumed traumatic expulsion of an anterior chamber intraocular lens two weeks postoperatively. The 59-year-old patient presented complaining of foreign-body sensation; we found the intraocular lens in his superior conjunctival fornix.

High altitude corneal endothelial decompensation.

A 77-year-old patient with low endothelial cell counts sustained acute unilateral endothelial decompensation when he traveled to an elevation of 12,500 feet. The corneal edema gradually increased after his return to sea level, and penetrating keratoplasty was required to restore vision. To our knowledge, this is the first reported case of hypoxia-induced corneal endothelial decompensation.

Posterior capsule opacification following phacoemulsification.

In a series of 200 consecutive senescent cataracts treated with phacoemulsification, 167(83.5%) were left with an intact posterior capsule at the initial surgery. Subsequently 35% developed an opacified capsule; the incidence rose to 50% in those patients followed for more than three years postoperatively. Polishing the posterior capsule did not prevent or delay the opacification. A secondary capsulotomy was performed in 56 cases with the Haab discission knife; no complications were directly associated with the technique.

Complications of phacoemulsification.

Charles Kelman performed the first phacoemulsification operation in 1967, but it was not until 1971 that the technique had been sufficiently refined to allow its use by others. Now over 2,000 surgeons have been trained in the technique, and more than 100,000 cases have been performed. However, extended follow-up in any given series has been difficult because of the wide geographic distribution of patients, and interpretation is hampered by the frequent insertion of intraocular lenses in these patients. The present series attempts to carefully document operative and postoperative complications encountered in a consecutive series of patients whose senile cataracts were treated by phacoemulsification.

Voluntary nystagmus.

Voluntary nystagmus is a pendular, rapid, conjugate, primarily horizontal, benign nystagmus initiated and maintained by voluntary effort. The amplitude is variable, but always low. The rate is constant and rapid. Convergence is variable--apparently essential in some, nonessential in others, but related in all of our cases. This condition appears to have a familial component and is more common than originally thought. Voluntary nystagmus should be considered when dealing with any patient exhibiting nystagmus in order to minimize the possibility of misdiagnosis as occurred in one of our cases.

Traumatic "pseudoprolapse" of orbital tissues into the maxillary antrum: a diagnostic pitfall.

Orbital trauma may result in what we term "pseudoprolapse" of orbital tissues: a subperiosteal, submucosal, or intramucosal hemorrhage which creates a balloon-like elevation of periosteum or maxillary sinus mucosa or both associated with a nondisplaced fracture or in some cases no fracture of the orbital floor. This occasionally causes an erroneous radiographic diagnosis indicating a blowout fracture with prolapse of orbital tissues, resulting in unnecessary surgery.