A cellular solid model of the lamina cribrosa: mechanical dependence on morphology.

The biomechanics of the optic nerve head (ONH) may underlie many of the potential mechanisms that initiate the characteristic vision loss associated with primary open angle glaucoma. Therefore, it is important to characterize the physiological levels of stress and strain in the ONH and how they may change in relation to material properties, geometry, and microstructure of the tissue. An idealized, analytical microstructural model of the ONH load bearing tissues was developed based on an octagonal cellular solid that matched the porosity and pore area of morphological data from the lamina cribrosa (LC). A complex variable method for plane stress was applied to relate the geometrically dependent macroscale loads in the sclera to the microstructure of the LC, and the effect of different geometric parameters, including scleral canal eccentricity and laminar and scleral thickness, was examined. The transmission of macroscale load in the LC to the laminar microstructure resulted in stress amplifications between 2.8 and 24.5xIOP. The most important determinants of the LC strain were those properties pertaining to the sclera and included Young's modulus, thickness, and scleral canal eccentricity. Much larger strains were developed perpendicular to the major axis of an elliptical canal than in a circular canal. Average strain levels as high as 5% were obtained for an increase in IOP from 15 to 50 mm Hg.

Image analysis of optic nerve disease.

Existing methodologies for imaging the optic nerve head surface topography and measuring the retinal nerve fibre layer thickness include confocal scanning laser ophthalmoscopy (Heidelberg retinal tomograph), optical coherence tomography, and scanning laser polarimetry. For cross-sectional screening of patient populations, all three approaches have achieved sensitivities and specificities within the 60-80th percentile in various studies, with occasional specificities greater than 90% in select populations. Nevertheless, these methods are not likely to provide useful assistance for the experienced examiner at their present level of performance. For longitudinal change detection in individual patients, strategies for clinically specific change detection have been rigorously evaluated for confocal scanning laser tomography only. While these initial studies are encouraging, applying these algorithms in larger numbers of patients is now necessary. Future directions for these technologies are likely to include ultra-high resolution optical coherence tomography, the use of neural network/machine learning classifiers to improve clinical decision-making, and the ability to evaluate the susceptibility of individual optic nerve heads to potential damage from a given level of intraocular pressure or systemic blood pressure.

Anterior scleral canal geometry in pressurised (IOP 10) and non-pressurised (IOP 0) normal monkey eyes.

AIMS: To characterise lamina cribrosa and anterior scleral canal wall architecture in pressurised (IOP 10 mm Hg) and non-pressurised (IOP 0 mm Hg) normal monkey eyes. METHODS: Eight normal eyes from eight monkeys were enucleated before sacrifice and the optic nerve heads (ONH) trephined and immersion fixed in glutaraldehyde (IOP 0). Nine normal eyes from nine monkeys were perfusion fixed in situ with paraformaldehyde at IOP 10 mm Hg (IOP 10), and the ONHs trephined and stored in glutaraldehyde. Each ONH specimen was embedded in glycol methacrylate and cut into vertical or horizontal, 4 micro m thick, serial sections. Within digitised images of every sixth section, anterior laminar position and laminar thickness were measured at nine evenly spaced locations across the scleral canal opening. Additionally, scleral canal diameters at Bruch's membrane (SCD-B) and at the anterior laminar insertion (SCD-ALI) were measured within the 15 middle section images of each vertically sectioned ONH. RESULTS: Anterior laminar position was significantly more anterior (nearer Bruch's membrane) in the IOP 10 eyes, compared with the IOP 0 eyes (116 (+/-95% CI; 2) micro m v 184 (2) micro m, respectively). Also in the IOP 10 eyes, the lamina cribrosa was thinner (195 (2) micro m v 264 (2) micro m) and the scleral canal diameter was larger (SCD-B: 1751 (23) micro m v 1591 (19) micro m; SCD-ALI: 1961 (21) micro m v 1717 (17) micro m), compared with the IOP 0 eyes. CONCLUSION: The anterior scleral canal wall is expanded and the lamina cribrosa is thinned and more tautly stretched within pressurised (perfusion fixed at IOP 10) young monkey eyes, compared with non-pressurised (immersion fixed at IOP 0) young monkey eyes. The constricted scleral canal and the relaxed and thickened lamina in the non-pressurised eyes may represent phenomena that contribute to optic disc swelling in hypotonous eyes.

Posterior scleral thickness in perfusion-fixed normal and early-glaucoma monkey eyes.

PURPOSE: To characterize posterior scleral thickness in the normal monkey eye and to assess the effects of acute (15- to 80-minute) and short-term chronic (3- to 7-week) intraocular pressure (IOP) elevations. METHODS: Both eyes of four normal monkeys (both eyes normal) and four monkeys with early glaucoma (one eye normal and one eye with induced chronic elevation of IOP) were cannulated. In each monkey, IOP was set to 10 mm Hg in the normal eye and 30 or 45 mm Hg in the contralateral eye (normal or early glaucoma) for 15 to 80 minutes. All eight monkeys were perfusion fixed, yielding eight low IOP-normal eyes, four high IOP-normal eyes, and four high IOP-early glaucoma eyes. Posterior scleral thickness was measured histomorphometrically at 15 measurement points within each eye, and the data were grouped by region: foveal, midposterior, posterior-equatorial, and equatorial. RESULTS: Overall, posterior scleral thickness was significantly different in the various regions and among the treatment groups (P < 0.0001). In the low IOP-normal eyes, the posterior sclera was thickest in the foveal region (307 microm) and thinner in the midposterior (199 microm), posterior-equatorial (133 microm), and equatorial (179 microm) regions. In the high IOP-normal and high IOP-early glaucoma eyes, the posterior sclera was thinner both overall and within specific regions, compared with the low IOP-normal eyes. CONCLUSIONS: The posterior sclera in the perfusion-fixed normal monkey eye thins progressively from the fovea to the equator and is thinnest just posterior to the equator. Acute and short-term chronic IOP elevations cause regional thinning within the posterior sclera of some monkey eyes, which significantly increases stresses in the scleral wall.

Slow release of the antimetabolite 5-fluorouracil (5-FU) from modified Baerveldt glaucoma drains to prolong drain function.

Drainage devices are routinely placed in the eyes of patients with glaucoma to reduce intraocular pressure (IOP) by providing controlled outflow of fluid (aqueous humor) via a filtering bleb. However, the natural wound healing response often interferes with fluid outflow by thickening the walls of the bleb over time, so that these devices rarely remain functional for more than 5 years. We investigated the use of controlled release of an antimetabolite, 5-fluorouracil (5-FU), within glaucoma drains to determine if the wound healing response could be reduced and the useful life span of the device increased. Collagen plugs containing 1.125 mg of 5-FU were placed in the silicone tubes of modified Baerveldt glaucoma drains. Eight drains with 5-FU and eight drains without 5-FU were implanted in one eye each of 16 New Zealand white rabbits: the contralateral eyes served as unoperated controls. Results were evaluated in terms of IOP, fibrous capsule thickness, macrophage density. and presence of type III collagen surrounding the drain plate, 3 and 6 months after implantation. In general, eyes implanted with antimetabolite-containing drains demonstrated significantly lower values for all evaluated parameters at 3 months and lower or equal values at 6 months, compared with the eyes not receiving 5-FU and the unoperated controls, indicating improved IOP-lowering function, reduced bleb wall thickness, and earlier achievement of a steady-state wound healing response. All eyes remained healthy throughout the 6-month duration of the study with no cytotoxicity complications in any of the eyes. Thus, biodegradable plugs placed within the silicone tubes of glaucoma drains can safely deliver 5-FU to filtering blebs over time, which could prolong the functional life of the bleb by decreasing the thickness of the anterior fibrous capsule and permitting sufficient fluid outflow to reduce IOP to physiological levels.

Optic disc surface compliance testing using confocal scanning laser tomography in the normal monkey eye.

PURPOSE: To determine the effect of acute, experimentally increased intraocular pressure on deformation of the surface of the optic nerve head (optic nerve head surface compliance testing) in normal monkey eyes using confocal scanning laser tomography. METHODS: A total of 156 compliance tests were performed on 48 normal eyes of 30 monkeys in three separate studies. Compliance testing involved obtaining confocal scanning laser tomographic images using a 10 degrees and/or 15 degrees and/or 20 degrees scan angle at various times after intraocular pressure was raised from 10 to 30 or 45 mm Hg. At each point, six images were analyzed to provide a value for a parameter, called mean position of the disc, which was used to express the amount of deformation the surface of the optic nerve head had undergone at that point. Statistical analysis (ANOVA) was performed to evaluate differences in the amounts of deformation in individual eyes at different intraocular pressures and at different compliance testing sessions (studies 1 and 2) and in the two eyes of individual monkeys under the same conditions (study 3). RESULTS: The majority of eyes showed posterior deformation of the surface of the optic nerve head ranging from 15 to 86 microm as early as 10 minutes after intraocular pressure was increased from 10 to 30 mm Hg. When pressure was increased from 30 to 45 mm Hg in a subset of these eyes, most showed additional deformation. Of the 12 eyes for which both 15 degrees and 20 degrees images were obtained at the same compliance test, 7 showed larger amounts of deformation in the 20 degrees images. Of the 18 monkeys tested in both eyes, 12 showed some differences and 4 showed substantial differences between the two eyes. CONCLUSIONS: In the normal monkey eye, the surface of the optic nerve head deforms rapidly (in as few as 10 minutes) in response to increased intraocular pressure. The amount of deformation varies between subjects and even within the two eyes of individual monkeys. Increasing the scan angle from 15 degrees to 20 degrees frequently increases the amount of deformation detected, suggesting that the peripapillary sclera and the optic nerve head may be involved in the deformation in some eyes.

Expanded polytetrafluoroethylene reinforcement material in glaucoma drain surgery.

PURPOSE: To determine whether a synthetic material, expanded polytetrafluoroethylene (E-PTFE), can be used successfully as a reinforcement material over the tubes of glaucoma drainage implants. METHODS: Patches of E-PTFE were sutured over the tubes of Baerveldt glaucoma drains implanted in the eyes of New Zealand white rabbits. Two material thicknesses were tested: 0.5 mm in four eyes and 0.25 mm in five eyes. Rabbit donor scleral patches were used in five eyes as the control. Total ocular health and intraocular pressure were monitored every 2 weeks after the procedure. Six months after implantation, the eyes were harvested and analyzed histologically. RESULTS: Two of the four eyes that received 0.5-mm thick E-PTFE patches showed some conjunctival melting over the anterior corners of the material close to the limbus. All five eyes that received 0.25-mm thick E-PTFE patches showed a healthy cellular wound healing response and no conjunctival melting. Cellular infiltration and collagen deposition in the E-PTFE materials showed integration of the patch material into the surrounding tissue. In the control eyes, marked thinning and resorption of the donor sclera immediately above the drainage tube was noted. CONCLUSION: Thin (0.25 mm) E-PTFE patches were well tolerated in all rabbit eyes tested. Thin E-PTFE should be investigated further as a functional alternative to donor sclera for reinforcement in glaucoma drain surgery.

The optic nerve head as a biomechanical structure: initial finite element modeling.

PURPOSE: To study the relationship between intraocular pressure (IOP) and the IOP-related stress (force/cross-sectional area) it generates within the load-bearing connective tissues of the optic nerve head. METHODS: Thirteen digital, three-dimensional geometries were created representing the posterior scleral shell of 13 idealized human eyes. Each three-dimensional geometry was then discretized into a finite element model consisting of 900 constituent finite elements. In five models, the scleral canal was circular (diameters of 0.50, 1.50, 1.75, 2.00, and 2.56 mm), with scleral wall thickness (0.8 mm) and inner radius (12.0 mm) held constant. In three models, the canal was elliptical (vertical-to-horizontal ratios of 2:1 [2.50 x 1.25 mm], 1.5:1 [2.1 x 1.4 mm], and 1.15:1 [1.92 x 1.67 mm]), with the same constant scleral wall thickness and inner radius. In five additional models, scleral canal size was held constant (1.92 x 1.67 mm), and either scleral wall thickness (three models, 0.5, 1.0, and 1.5 mm) or inner radius (two models, 13.0 and 14.0 mm) was varied. In all models, each finite element was assigned a single isotropic material property, either scleral (modulus of elasticity, 5500 kPa) or axonal (modulus of elasticity, 55 kPa). Maximum stresses within specific regions were calculated at an IOP of 15 mm Hg (2000 Pa). RESULTS: Larger scleral canal diameter, elongation of the canal, and thinning of the sclera increased IOP-related stress for a given level of IOP. For all models, maximum IOP-related stress ranged from 6 x IOP (posterior sclera) to 122 x IOP (laminar trabeculae). For each model, maximum IOP-related stress was highest within the laminar trabecular region and decreased progressively through the laminar insertion, peripapillary scleral, and posterior scleral regions. Varying the inner radius had little effect on the maximum IOP-related stress within the scleral canal. CONCLUSIONS: Initial finite element models show that IOP-related stress within the load-bearing connective tissues of the optic nerve head is substantial even at low levels of IOP. Although the data suggest that scleral canal size and shape and scleral thickness are principal determinants of the magnitude of IOP-related stress within the optic nerve head, models that incorporate physiologic scleral canal and laminar geometries, a more refined finite element model meshwork, and nonisotropic material properties will be required to confirm these results.

Biocompatibility response to modified Baerveldt glaucoma drains.

Glaucoma implants are designed to increase fluid outflow from the eye in order to decrease intraocular pressure and prevent damage to the optic nerve. The implant consists of a silicone tube that is inserted into the anterior chamber at one end and is attached at the other end to a silicone plate that is sutured to the outside of the globe beneath the conjunctiva. The glaucoma "implant" becomes a "drain" over the first 3 to 6 postoperative weeks as the silicone plate is enclosed by a fibrous capsule that allows a space to form into which fluid can drain and from which fluid can be absorbed by the surrounding tissues. Ideally, the size and thickness of the capsule (the filtering bleb) that surrounds the plate is such that the amount of fluid that passes through the capsule is identical to the amount of fluid produced by the eye at an intraocular pressure of 8 to 14 mmHg. The most common long-term complication of these implants is failure of the filtering bleb 2 to 4 years after surgery due to the formation of a thick fibrous capsule around the device. Micromovement of the smooth drainage plate against the scleral surface may be integral to the mechanism of glaucoma implant failure by stimulating low-level activation of the wound healing response, increased collagen scar formation, and increased fibrous capsule thickness. To test this hypothesis, we modified seven Baerveldt implants by adding porous cellular ingrowth material to the posterior surface of the drainage plate. Seven modified and five unmodified implants were placed in adult rabbit eyes. After 6 months, we found that the fibrous capsule around the modified implants was significantly thinner than the capsule surrounding the unmodified implants (p < 0.05), particularly on the surface between the porous ingrowth material and the sclera (p < 0.05). Although type I collagen predominated in the fibrous capsules around both types of implants, the amount of type III collagen in the capsules around the modified implants was significantly less than the amount around the unmodified implants (p < 0.05). We believe that these data suggest a reduction in the wound healing response to the modified implants, with greater stability of capsule thickness. Long-term studies are needed to verify that the stability of the capsules around the modified implants persists over a period of years, in which case this type of modification may prove useful in prolonging the functional life of these devices in the surgical treatment of glaucoma.

Measurement of optic disc compliance by digitized image analysis in the normal monkey eye.

PURPOSE: To characterize the compliance of the normal monkey optic disc under conditions of induced short-term fluctuations in intraocular pressure (IOP). METHODS: In 10 monkeys, one eye was compliance tested on three separate days followed by a single test of the contralateral eye (40 compliance tests). In a testing session, the optic disc was imaged at 2 and 47 minutes (baseline time point) after IOP was lowered to 10 mmHg; then at 2, 17, 32, and 47 minutes after IOP was elevated to 45 mmHg; then at 2, 47, and, in some cases, 92 minutes after IOP was lowered back to 10 mmHg. Eight digitized images were analyzed at each time point, yielding two parameters to characterize the position of the disc: the Mean Position of the Disc (MPD) and the Change from MPDBaseline (the value of MPD at a given time point minus the value for MPD at the baseline time point of that testing session). Analysis of variance (ANOVA) testing was used to evaluate the overall effect of IOP on both parameters while taking into account the effects of variability due to different monkeys and repetitions of the test as well as differences between the two eyes of an individual monkey. With the addition of data from 11 compliance tests performed on eight additional monkeys, the overall results were calculated in terms of the mean Change from MPDBaseline at each time point for a total of 51 compliance testing sessions. RESULTS: The mean Change from MPDBaseline was -28 microns (95% confidence interval, -23 to -33 microns) 47 minutes after elevation of IOP. The disc surface returned to its baseline position 92 minutes after IOP was lowered back to 10 mmHg. Elevation of IOP within a compliance test had a significant effect on the position of the optic disc surface (P = 0.0002, ANOVA), as characterized by the parameter Change from MPDBaseline. Neither the difference in the amount of movement between the two eyes of an individual monkey nor the variability within the three repetitions of the test in a given eye was statistically significant. CONCLUSION: Small, reversible (elastic) posterior deformations of the optic disc surface follow acute elevations of IOP in the normal monkey eye. Detection of acute IOP-induced deformations of the optic disc surface may represent a means by which to mechanically test the deeper load-bearing tissues of the optic nerve head.

Early changes in optic disc compliance and surface position in experimental glaucoma.

PURPOSE: To detect changes in the compliance and baseline position (position at the baseline time point of a compliance test) of the monkey optic disc after the onset of chronic experimental glaucoma. METHODS: Sixty-six compliance tests were performed on 26 eyes of 13 monkeys. Longitudinal Study. In seven normal monkeys, compliance tests were performed three times in one eye (study eye) and once in the contralateral eye. In the study eye of five of these monkeys, chronic experimental glaucoma was then induced and compliance tests were performed at some or all of the following postglaucoma testing intervals: 1 to 2 weeks, 3 to 4 weeks, 5 to 8 weeks, 9 to 12 weeks, 13 to 18 weeks, and more than 18 weeks after the onset of elevated intraocular pressure (IOP). In the study eye of the remaining two monkeys, the optic nerve was transected, and compliance was tested at 5, 9, and 13 weeks after transection. An analysis of variance (ANOVA) was performed to detect an increase (hypercompliance) or decrease (rigidity) in the compliance of the glaucomatous eyes at each testing interval. A second ANOVA was performed to detect the onset of chronic posterior deformation of the baseline position of each disc. Cross-Sectional Study. In six additional monkeys with pre-existing experimental glaucoma, the glaucomatous study eye was compliance tested at one of the postglaucoma testing intervals used in the longitudinal study. The contralateral normal eye was compliance tested once. These data were then added to the data from the five longitudinally studied monkeys at the appropriate preglaucoma and postglaucoma testing intervals. A third ANOVA was done to compare the compliance of the expanded group of glaucomatous eyes at each postintervention testing interval with the compliance of the 13 normal contralateral eyes. RESULTS: Compliance. In the longitudinally (Pr > F = 0.0005) and cross-sectionally (Pr > F = 0.0001) studied glaucomatous eyes, optic disc compliance increased significantly by 1 to 2 weeks and then returned to a level statistically indistinguishable from normal within 13 to 18 weeks after the onset of glaucoma. In the transection eyes, the optic discs were significantly less compliant (more rigid) at 5 and 9 weeks after transection compared with the discs in either the normal or the glaucomatous eyes (Pr > F < 0.05). Baseline Optic Disc Position. Chronic posterior deformation of the disc was detected in one of three eyes tested 1 to 2 weeks and three of four eyes tested 3 to 4 weeks after the onset of glaucoma (Pr > F < 0.05). Chronic posterior deformation was not detected in the discs of either of the transection eyes at any of the post-transection testing intervals. CONCLUSION: Changes in optic disc compliance and surface position were detected by digitized image analysis within 2 to 4 weeks of the onset of experimental glaucoma in the monkey eye. These findings are unlikely to be due to axon loss alone, because they did not occur in optic nerve transection eyes (which constitute a model of axon loss in which intraocular pressures remain normal). The results suggest that IOP-related damage to the load-bearing connective tissues of the optic nerve head may occur early in the course of experimental glaucoma.

Comparison of clinician judgment with digitized image analysis in the detection of induced optic disk change in monkey eyes.

PURPOSE: To compare the ability of clinicians to detect change in the photographic appearance of the optic disk with the performance of a system for digitized image analysis. METHODS: In 11 monkey eyes, a Topcon Imagenet System was used to acquire eight digitized image pairs and four stereoscopic photographs at an intraocular pressure of 10 mm Hg, and then, again, 45 minutes after intraocular pressure was increased to 45 mm Hg. We recently reported detection of global (ten of 11 eyes) and regional (11 of 11 eyes) change in the digitized images of these eyes by using two new statistical strategies for optic disk analysis. For the current study, we evaluated the ability of three clinicians (the authors) to detect a change within the stereoscopic photographs of these 11 optic disks. For each eye, the eight stereoscopic photographs (four at intraocular pressure of 10 mm Hg and four at intraocular pressure of 45 mm Hg) were developed as stereoscopic slides and arranged into four pairs (10/10, 45/45, 10/45, and 45/10 mm Hg). Thus, two pairs represented no change in intraocular pressure (10/10 and 45/45 mm Hg) and the other two pairs represented either an increase or a decrease in intraocular pressure (10/45 and 45/10 mm Hg). The 44 pairs of stereoscopic slides (four pairs for each of 11 eyes) were masked then randomly mixed. On two separate occasions, each clinician evaluated each pair of stereoscopic slides for the presence of absence of optic disk change. RESULTS: Reproducibility between the two readings of each clinician ranged from .50 to .64 (kappa statistic). Clinicians correctly detected change (as detected by image analysis) within 45% to 64% of the 10/45 and 45/10 pairs of stereoscopic slides. Clinicians correctly indentified no change within 86% to 100% of the 10/10- and 45/45-mm Hg pairs of stereoscopic slides. Clinicians correctly identified no change significantly more often than change (P < .01, chi 2 test). Change was not detected consistently by all three clinicians in any of the 11 eyes. CONCLUSION: In a controlled experimental setting, digitized image acquisition with extensive secondary statistical analysis more sensitively detected small short-term changes in the surface of the optic disks of monkeys than did three masked clinicians.

Early clinical experience with the Baerveldt implant in complicated glaucomas.

PURPOSE: To evaluate our early experience with the Baerveldt implant in patients with complicated glaucoma. METHODS: We reviewed the charts of all patients with more than six months of follow-up after placement of a Baerveldt implant at LSU Eye Center. Surgery was considered a success if intraocular pressure was 21 mm Hg or less (with or without antiglaucoma medications) at the last postoperative visit, except when further glaucoma surgery had been performed or when loss of light perception occurred. RESULTS: Fifty eyes (50 patients) were divided into six diagnostic groups, with mean follow-up times of 16.1 to 19.2 months. Success was achieved in 36 of 50 patients (72%): 26 of 35 (74%) patients with aphakia or pseudophakia, nine of 12 (75%) patients with previously failed filtering surgery, three of seven patients with neovascular glaucoma, all three patients under the age of 13 years, nine of 13 (69%) patients who underwent penetrating keratoplasty, and four of five phakic patients. Overall, visual acuity improved or remained within one line of the preoperative acuity in 32 (64%) patients. The most frequently observed short- and long-term complications were serous choroidal effusion associated with hypotony in 13 (26%) patients and corneal graft failure in six of 13 (46%) corneal transplant patients, respectively. CONCLUSION: Within the study follow-up time, the Baerveldt implant appeared to be safe and effective, with success rates for intraocular pressure control similar to those reported in a recent retrospective study of the Molteno implant.

Cloning and characterization of rod opsin cDNA from the Old World monkey, Macaca fascicularis.

PURPOSE: Opsin sequences from different phyla have been compared to examine the structural and functional regions of this molecule and to assess the molecular evolution of genes in the animal kingdom. Of all the sequences reported, there is only one primate sequence (human) for rod opsin. To extend our knowledge of the primate family of opsins, the authors cloned and characterized the opsin cDNA for the Old World monkey Macaca fascicularis and determined its position in the phylogenetic tree of the opsin gene family. METHODS: A fragment of the monkey opsin cDNA was generated using specific primers and the polymerase chain reaction. This fragment was then used as a probe to isolate several cDNA clones from a M. fascicularis retinal cDNA library. The nucleotide sequence of monkey opsin was determined and translated into an amino acid sequence. The amino acid sequences of opsins from a variety of organisms ranging from mollusks, arthropods, and vertebrates, including monkey, were then compared to identify highly conserved amino acid residues and to construct a phylogenetic tree of the rod opsins. RESULTS: The monkey has a single major 2.2-kb transcript for opsin and minor transcripts of 1.5, 4.8, and 8.9 kb. The major transcript is highly abundant in the monkey retina and is localized to the inner segments of rod photoreceptor cells, typical of opsin mRNAs in other organisms. The sequence of monkey opsin closely resembles the human sequence at the nucleotide and the amino acid levels, with the latter having only 7 differences out of 348 residues. Comparison of the monkey sequence with the amino acid sequences from diverse organisms shows that all opsins share only 34 conserved amino acids, with the highest concentration of these residues occurring in the first cytoplasmic loop of rhodopsin. A hypothetical phylogenetic tree of the opsins suggests that both human and monkey opsin shared an ancestral gene with the mammalian Order Carnivora. CONCLUSION: The opsins of man and Old World monkeys have diverged little from the time they shared a common ancestor. Comparison of opsins from diverse phyla, however, shows that only 34 residues have been conserved. These conserved residues are likely to be important in the structure and function of rhodopsin.

Applications for a corneal mattress suture in anterior limbal wound repairs.

We describe the use of a corneal mattress suture to manage two complications of trabeculectomy: first, to repair an anterior conjunctival tear/disinsertion in a limbus-based conjunctival flap; and, second, to restore wound integrity by reinforcing a focal section of scleromalacia or to close a perforation remaining from a previous cataract wound encountered during complicated trabeculectomy. In each setting, a single, double-armed 10-0 nylon corneal mattress suture is used as an anchor to establish a watertight limbal-wound closure. Additionally, for repairing an area of a scleromalacia/perforation, the corneal mattress suture can be used to incorporate a graft of Tenon's fascia into the wound.

Global and regional detection of induced optic disc change by digitized image analysis.

OBJECTIVE: To evaluate two new strategies for the detection of optic disc change within individual eyes by digitized image analysis. METHODS: Eleven normal optic discs of 11 monkeys were imaged with a digital imaging system (Topcon Imagenet, Topcon Instrument Corporation of America, Paramus, NJ) at two intraocular pressures (10 and 45 mm Hg). To detect global change in the disc, we compared conventional optic disc parameters with a new optic disc parameter: mean position of the disc. To detect regional change, the 95% confidence interval for change was calculated for each data point and mapped for each disc. RESULTS: Posterior deformation of the disc surface was detected in seven of 11 eyes using conventional parameters and in 10 of 11 eyes using mean position of the disc. Regions of posterior deformation were detected by 95% confidence interval for change mapping in all 11 discs as localized areas of confluent, posteriorly displaced points. CONCLUSIONS: Mean position of the disc outperformed conventional measurements in the detection of global optic disc change. Ninety-five percent confidence interval for change mapping may allow individual data point-based focal and regional analysis of the disc.

Tuberculin skin-test-induced uveitis in the absence of tuberculosis.

A 16-year-old Caucasian girl who showed no evidence of tuberculosis or other systemic disease developed acute panuveitis progressing to bilateral serous retinal detachments following purified protein derivative (PPD) skin testing on two separate occasions separated by an interval of 8 years. Both episodes responded rapidly to steroid therapy. Uveal hypersensitivity to PPD skin testing has been described in the presence of ocular or systemic tuberculosis, Eales' disease, and the Vogt-Koyanagi-Harada syndrome (VKH). Our case, however, suggests that profound uveitis may be precipitated by routine PPD skin testing alone.

Comparison of hemoglobin Köln erythrocyte membranes with malondialdehyde-reacted normal erythrocyte membranes.

Splenectomized patients with hemoglobin (Hb) Köln have rigid RBCs with membrane polypeptide aggregates that are not dissociable with disulfide-reducing agents. Malondialdehyde (MDA) action on normal RBCs produced rigid RBCs with similar nondissociable aggregates. To test the hypothesis that Hb Köln RBC aggregates contained unsaturated MDA-type bonds, we reduced normal control RBC membranes, Hb Köln RBC membranes, and MDA-reacted membranes with [3H]NaBH4. Hb Köln RBC membranes and MDA-reacted membranes both had significantly more 3H incorporation than control membranes. Furthermore, 3H incorporation in both Hb Köln and MDA-treated membranes was located in the membrane polypeptide aggregates, presumably saturating the crosslinking bonds. After reaction of RBCs with [14C]MDA, the MDA label was similarly concentrated in the membrane polypeptide aggregates. Normal RBC membranes incubated with MDA were analyzed with and without reduction by NaBH4 prior to amino acid determination by high-performance liquid chromatography (HPLC). Reduction with NaBH4 after MDA treatment decreased the lysyl residues by 33% and the serine by 7% and increased by 10% the methionyl residues, but did not affect 12 other amino acids. Similar changes could be detected in NaBH4-reduced Hb Köln aggregates in methionine and serine content. MDA may also alter protein configuration, as evidenced by an increase in the protease susceptibility of membrane proteins from MDA-treated and Hb Köln RBCs. We conclude that Hb Köln RBC membranes, like MDA-treated membranes, have similar high molecular weight aggregates conferring decreased membrane deformability, [3H]NaBH4-reducible unsaturated bonds, changes in amino acid composition upon reduction, and protease-sensitive configurational changes.