Search

Purpose To elucidate the dynamic accommodative movements of the lens capsule, posterior lens and the strand that attaches to the posterior vitreous zonule insertion zone and posterior lens equator (PVZ INS-LE), and their age-related changes. Methods Twelve human subjects (ages 19–65 years) and 12 rhesus monkeys (ages 6–27 years) were studied. Accommodation was induced pharmacologically (humans) or by central electrical stimulation (monkeys). Ultrasound biomicroscopy was used to image intraocular structures in both species. Surgical procedures and contrast agents were utilized in the monkey eyes to elucidate function and allow visualization of the intraocular accommodative structures. Results Human: The posterior pole of the lens moves posteriorly during accommodation in proportion to accommodative amplitude and ciliary muscle movement. Monkey: Similar accommodative movements of the posterior lens pole were seen in the monkey eyes. Following extracapsular lens extraction (ECLE), the central capsule bows backward during accommodation in proportion to accommodative amplitude and ciliary muscle movement, while the peripheral capsule moves forward. During accommodation the ciliary muscle moved forward by ~1.0 mm, pulling forward the vitreous zonule and the PVZ INS-LE structure. During the accommodative response the PVZ INS-LE structure moved forward when the lens was intact and when the lens substance and capsule were removed. In both the monkey and the human eyes these movements declined with age. Conclusions The accommodative shape change of the central capsule may be due to the elastic properties of the capsule itself. For these capsule/lens accommodative posterior movements to occur, the vitreous face must either allow for it or facilitate it. The PVZ INS-LE structure may act as a ‘strut’ to the posterior lens equator (pushing the lens equator forward) and thereby facilitate accommodative forward lens equator movement and lens thickening. The age-related posterior restriction of the ciliary muscle, vitreous zonule and the PVZ-INS LE structure dampens the accommodative lens shape change. Future descriptions of the accommodative mechanism, and approaches to presbyopia therapy, may need to incorporate these findings.

Purpose The purpose of this study is to evaluate effects of vitrectomy (PPV) and lens extraction with intraocular lens implantation (PE/IOL) on molecular oxygen (pO2) distribution, aqueous humor antioxidant-oxidant balance, aqueous humor dynamics, and histopathologic changes in the trabecular meshwork (TM) in the older macaque monkey. Methods Six rhesus monkeys underwent PPV followed by PE/IOL. pO2, outflow facility, and intraocular pressure (IOP) were measured. Aqueous and vitreous humor specimens were analyzed for antioxidant status and 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative damage. TM specimens were obtained for immunohistochemical and quantitative PCR analysis. Results pO2 at baseline revealed steep gradients in the anterior chamber and low levels in the posterior chamber (PC) and around the lens. Following PPV and PE/IOL, pO2 significantly increased in the PC, around the IOL, and angle. IOP increased following both surgical interventions, with no change in outflow facility. Histopathologic analysis did not show changes in TM cell quantification, but there was an increase in 8-OHdG. Quantitative PCR did not reveal significant differences in glaucoma-related gene expression. Aqueous and vitreous humor analysis revealed decreased ascorbate and total reactive antioxidant potential and increased 8-OHdG in the aqueous humor only in the surgical eyes. Conclusions Oxygen distribution in the older rhesus monkey is similar to humans at baseline and following surgical interventions. Our findings of histopathologic changes of TM oxidative damage and alterations in the oxidant-antioxidant balance suggest a potential correlation of increased oxygen exposure with oxidative stress/damage and the development of open angle glaucoma.

This study is aimed to determine if the serine-threonine kinase inhibitor H-7 inhibits secondary cataract after phacoemulsification in the live rabbit eye.Eighteen rabbits underwent extracapsular lens extraction by phacoemulsification in 1 eye. The eye was treated with intravitreal H-7 (300 or 1,200 μM; n = 6 or 5) or balanced salt solution (BSS) (n = 7) immediately after the surgery and twice weekly for 10 weeks. Each eye received slit lamp biomicroscopy once a week, during which posterior capsule opacification (PCO) was evaluated. The eye was then enucleated and the lens capsule was prepared, fixed, and imaged. PCO was evaluated again on the isolated lens capsule under a phase microscope. Soemmering's ring area (SRA) and the entire lens capsule area were measured from capsule images on a computer and the percentage of SRA (PSRA) in the entire capsule area was calculated. Wet weight of the capsule (WW) was determined on a balance.No significant difference in PCO was observed in any comparison. No significant differences in SRA, PSRA, and WW were observed between the 300 μM H-7-treated eye and the BSS-treated eye. However, SRA, PSRA, and WW in the 1,200 μM H-7-treated eye were significantly smaller than those in the BSS-treated eye [28.3 ± 16.2 vs. 61.4 ± 8.86 mm(2) (P = 0.001), 33% ± 20% vs. 65% ± 15% (P = 0.01), and 65.6 ± 27.9 vs. 127.0 ±37.3 mg (P = 0.01)].Intravitreal H-7 (1,200 μM) significantly inhibits Soemmering's ring formation in the live rabbit eye, suggesting that agents that inhibit the actomyosin system in cells may prevent secondary cataract after phacoemulsification.

Purpose To determine how surgically altering the normal relationship between the lens and the ciliary body in rhesus monkeys affects centripetal ciliary body and lens movement. Methods In 18 rhesus monkey eyes (aged 6-27 years), accommodation was induced before and after surgery by electrical stimulation of the Edinger-Westphal nucleus. Accommodative amplitude was measured by coincidence refractometry. Goniovideography was performed before and after intra- and extracapsular lens extraction (ICLE, ECLE) and anterior regional zonulolysis (ARZ). Centripetal lens/capsule movements, centripetal ciliary process (CP) movements, and circumlental space were measured by computerized image analysis of the goniovideography images. Results Centripetal accommodative CP and capsule movement increased in velocity and amplitude after, compared with before, ECLE regardless of age (n = 5). The presence of the lens substance retarded capsule movement by approximately 21% in the young eyes and by approximately 62% in the older eyes. Post-ICLE compared with pre-ICLE centripetal accommodative CP movement was dampened in all eyes in which the anterior vitreous was disrupted (n = 7), but not in eyes in which the anterior vitreous was left intact (n = 2). After anterior regional zonulolysis (n = 4), lens position shifted toward the lysed quadrant during accommodation. Conclusions The presence of the lens substance, capsule zonular attachments, and Wieger's ligament may play a role in centripetal CP movement. The capsule is still capable of centripetal movement in the older eye (although at a reduced capacity) and may have the ability to produce approximately 6 D of accommodation in the presence of a normal, young crystalline lens or a similar surrogate.

Recent reports from large clinical trials have clearly demonstrated that lowering intraocular pressure (IOP) in persons with ocular hypertension has a beneficial effect on reducing the progression of glaucomatous disease. Few studies of this effect have been conducted in controlled laboratory settings, however, none have been conducted using non-human primates, the model of experimental glaucoma considered most similar to the human disease. Using data collected retrospectively from a trabeculectomy study using 16 cynomolgous monkeys with experimental ocular hypertension, we evaluated both the threshold of elevated IOP required to cause clinically observable damage to the optic nerve head and also if lowering IOP below this threshold prevents further damage. An index of the level of elevated IOP experienced by experimental eyes (the Pressure Insult) was calculated as the slope of the difference in cumulative IOP between experimental and control eyes during four intervals of time over the course of the experiment, while damage to the optic nerve head was evaluated by measuring the Cup:Disc ratio for each eye from stereoscopic photographs taken at the end of each interval. An increase in the Cup:Disc ratio was significantly associated with both the maximum IOP obtained in the experimental eye during each interval (r = 0.573, P < 0.001) and the Pressure Insult (r = 0.496, P < 0.001). Pressure Insult values less than 11 mm Hg Days/Day were not associated with glaucomatous damage in monkey eyes, whereas values greater than 11 showed a significant correlation with increasing Cup:Disc ratios (P < 0.001). Trabeculectomy to reduce the Pressure Insult below 11 was correlated with an attenuation of the rate of progression of the Cup:Disc ratio in eyes that had exhibited damage before surgery. These results contribute further to our understanding of this model of experimental glaucoma by demonstrating a threshold at which IOP needs to be elevated to stimulate damage, while also providing corroborating evidence that lowering IOP in ocular hypertensive monkeys can attenuate the progression of glaucomatous disease.

Objectives To determine the incidence of late-onset bleb-related complications following trabeculectomy with mitomycin and to report the management and outcome of bleb leaks following trabeculectomy with mitomycin. Methods A retrospective medical record review of all patients who underwent trabeculectomy with mitomycin from June 1, 1991, through April 30, 1998, at our institution was performed. The Kaplan-Meier survival method was used to estimate the probability of (1) endophthalmitis, (2) blebitis, (3) a bleb leak, and (4) the combined outcome (the first occurrence of a bleb leak, blebitis, or endophthalmitis). This survival analysis included only the first trabeculectomy in an eye, with at least 3 months of follow-up during the study period. A separate description of bleb leak management and outcome was performed. Results Two hundred thirty-nine eyes of 198 patients were included in the survival analysis. The average follow-up was 2.7 (range, 0.3-7.3) years. Twenty eyes(8%) from 19 patients experienced a bleb leak; the adjusted incidence was 3.2% per patient-year. Five eyes (2%) had an episode of blebitis. Eight eyes(3%) experienced an episode of endophthalmitis; the follow-up adjusted incidence(number of events per patient-year) was 1.3%. Twenty-seven eyes (11%) from 26 patients had at least 1 of the complications of a bleb leak, blebitis, or endophthalmitis; the adjusted incidence was 4.4% per patient-year. A Kaplan-Meier analysis estimated the 5-year probability of developing a bleb leak, blebitis, or endophthalmitis to be 17.9%, 6.3%, and 7.5%, respectively. Two hundred fifty-eight trabeculectomies in 242 eyes of 198 patients were included in the description of bleb leak management and outcome. Bleb leaks occurred in 22 eyes (9% of the 258 trabeculectomies). Seventeen eyes were successfully treated with office-based measures, and 4 ultimately underwent surgical bleb revision. One eye without infection continued to leak after 11 months of office-based therapy. Conclusions There is significant morbidity associated with a trabeculectomy with mitomycin. The incidence of a bleb leak or an infection continues at a fairly constant rate over time, such that at 5 years, up to 23% of all patients might develop one of these complications. An isolated bleb leak seems to be a relatively benign condition, as three quarters resolve with office-based methods.

PURPOSE To determine the role of the lens and the lens capsule in the three-dimensional architecture of the ciliary muscle at rest and during accommodation, in live rhesus monkeys and in histologic sections, by removing the entire lens, or only the lens nucleus and cortex, while leaving the posterior capsule in place. METHODS In 15 rhesus monkey eyes, aged 6 to 27 years, accommodation was induced by central stimulation of the Edinger-Westphal nucleus before and after intra- or extracapsular lens extraction (ICLE, ECLE). Forward ciliary body movement and ciliary body width were measured by ultrasound biomicroscopy (UBM, 50 MHz). The monkeys were then killed, the eyes were examined morphologically in 1-microm sections, and the shape of the ciliary muscle was compared with that obtained from UBM images. RESULTS The shape of the ciliary muscle in eyes undergoing ECLE (n = 5) did not differ from that in control eyes. In contrast, after ICLE (n = 10), accommodative forward ciliary body movement (P < 0.01) and thickness were decreased (P < 0.001), length was increased (P = 0.058), and the inner apex was located more posteriorly than in control eyes (P < 0.005). Histologic and in vivo data were similar and showed that the ciliary muscle maintained its triangular shape only if the lens capsule (with or without the lens substance) was present. CONCLUSIONS The posterior lens capsule and anterior zonular attachments facilitate forward accommodative ciliary body movement. Lens substance extraction procedures that leave the posterior capsule intact, similar to those used clinically, do not affect the capsule/zonular/muscular system movements, an important finding for accommodating intraocular lens development.

PURPOSE The underlying causes of presbyopia, and the functional relationship between the ciliary muscle and lens during aging are unclear. In the current study, these relationships were studied in rhesus monkeys, whose accommodative apparatus and age-related loss of accommodation are similar to those in humans. METHODS Centripetal ciliary body and lens equator movements were measured during accommodation in 28 eyes of 21 rhesus monkeys (ages, 5.7-26 years) by goniovideography. Ultrasound biomicroscopy was performed in 21 eyes of 17 monkeys. Narrowing of the angle between the anterior aspect of the ciliary body and the inner aspect of the cornea was used as a surrogate indicator of forward ciliary body movement during accommodation. RESULTS Average centripetal ciliary body movement in older eyes (age > or =17 years, n = 16) was approximately 20% (0.09 mm) less than in young eyes (age, 6-10 years, n = 6), but not enough to explain the 60% (0.21 mm) loss in centripetal lens movement nor the 76% (10.2 D) loss in accommodative amplitude. Average forward ciliary body movement was 67% (49 degrees ) less in older (n = 11) versus young (n = 6) eyes. Maximum accommodative amplitude correlated significantly with the amplitude of centripetal lens movement (0.02 +/- 0.003 mm/D; n = 28; P < 0.001) and with forward ciliary body movement (3.34 +/- 0.54 deg/D; n = 21; P = 0.01). CONCLUSIONS Decreased lens movement with age could be in part secondary to extralenticular age-related changes, such as loss of ciliary body forward movement. Ciliary body centripetal movement may not be the limiting component in accommodation in the older eye.

Treatment of 45Ca2+-loaded GH3 pituitary cells with various concentrations of digitonin revealed discrete pools (I and II) of cellular 45Ca2+ defined by differing detergent sensitivities. Markers for cytosol and intracellular organelles indicated that the two 45Ca2+ pools were correlated with the two major cellular Ca2+-sequestering organelles, endoplasmic reticulum (I) and mitochondria (II). Studies with various inhibitors were consistent with these assignments. Mitochondrial uncouplers preferentially depleted 45Ca2+ pool II while trifluoperazine selectively depleted 45Ca2+ pool I. Control experiments indicated that translocation of in situ organellar 45Ca2+ during and after permeabilization was negligible. We used the digitonin-permeabilization method to examine the effect of thyrotropin-releasing hormone (TRH) treatment on intracellular Ca2+ pools of GH3 pituitary cells. TRH was found to rapidly deplete both endoplasmic reticulum and mitochondrial exchangeable Ca2+ by 25-30%. The 45Ca2+ loss from both pools was maximal by 1 min after TRH addition and was followed by a recovery phase; mitochondrial 45Ca2+ content returned to control levels by 30 min. Previous treatment of cells with the mitochondrial uncoupler carbonyl cyanide p-trifluoromethoxy-phenylhydrazone blocked TRH-induced 45Ca2+ efflux from mitochondria, while previous treatment with valinomycin, an agent that depleted both 45Ca2+ pools, blocked any additional effect of TRH on these pools. We conclude that TRH rapidly promotes a net loss of exchangeable Ca2+ from GH3 cells as a result of hormone-induced mobilization of Ca2+ from endoplasmic reticulum and mitochondria.