Serial multifocal electroretinograms during long-term elevation and reduction of intraocular pressure in non-human primates.

The purpose of this study was to evaluate the relationship between elevations of intraocular pressure (IOP) and the multifocal electroretinogram (mfERG) in non-human primates. Experimental glaucoma was induced in 4 rhesus and 4 cynomolgus monkeys by laser trabecular meshwork destruction (LTD) in one eye. To evaluate the contribution of ganglion cells to mfERG changes, one monkey of each species had previously underwent unilateral optic nerve transection (ONT). After >or=44 weeks of elevation, the IOP was reduced by trabeculectomy in 2 non-transected animals. In the intact (non-transected) animals, there was an increase in the amplitude of the early mfERG waveforms (N1 and P1) of the first-order kernel (K1) throughout the period of IOP elevation in all of the rhesus, but not all of the cynomolgus monkeys. A species difference was also present as a decrease of the second-order kernel, first slice (K2.1) in all of the cynomolgus monkeys but only in 1 of the rhesus monkeys (the 1 with the ONT). Similar IOP effects on the mfERG were seen in the ONT animals. Surgical lowering of IOP resulted in a return of the elevated K1 amplitudes to baseline levels. However, the depressed K2.1 RMS in the cynomolgus monkeys did not recover. These results demonstrate species-specific changes in cone-driven retinal function during periods of elevated IOP. These IOP-related effects can occur in the absence of retinal ganglion cells and may be reversible.

Effects of Vitrectomy and Lensectomy on Older Rhesus Macaques: Oxygen Distribution, Antioxidant Status, and Aqueous Humor Dynamics.

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.

Comparison of the Ahmed Glaucoma Valve, the Krupin Eye Valve with Disk, and the double-plate Molteno implant.

OBJECTIVE: To compare the efficacy of the nonvalved double-plate Molteno implant with two valved implants, the Krupin Eye Valve with Disc and the Ahmed Glaucoma Valve, in the treatment of recalcitrant glaucoma. PATIENTS AND METHODS: The authors performed a nonrandomized retrospective review of patients who received the Molteno implant (n = 27), Krupin Eye Valve with Disc (n = 13), or Ahmed Glaucoma Valve (n = 13), with adjunctive mitomycin C. RESULTS: Kaplan-Meier life-table analysis showed that the Molteno implant patients were more likely to maintain an intraocular pressure between 5 and 15 mm Hg than Ahmed Glaucoma Valve patients (P = 0.03). Success rates at 1 year were 80% (95% CI, 66-97%) for the Molteno implant, 39% (19-77%) for the Krupin Eye Valve with Disc, and 35% (15-82%) for the Ahmed Glaucoma Valve. However, Ahmed Glaucoma Valve patients were less likely to experience complications requiring reoperation or loss of two or more lines of visual acuity (P < 0.01) than Molteno implant or Krupin Eye Valve with Disc patients. CONCLUSIONS: This nonrandomized study suggests that the Molteno implant with mitomycin C is more likely to result in intraocular pressures in the lower teens than the Ahmed Glaucoma Valve with mitomycin C. The findings suggest that the Ahmed implant is less likely to create problems leading to reoperations or visual acuity loss than the Molteno or Krupin implants.

Effect of H-7 on secondary cataract after phacoemulsification in the live rabbit eye.

PURPOSE: This study is aimed to determine if the serine-threonine kinase inhibitor H-7 inhibits secondary cataract after phacoemulsification in the live rabbit eye. METHODS: 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. RESULTS: 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)]. CONCLUSIONS: 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.

Surgical intervention and accommodative responses, I: centripetal ciliary body, capsule, and lens movements in rhesus monkeys of various ages.

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.