Decreased carbohydrate metabolism enzyme activities in the glaucomatous trabecular meshwork.

PURPOSE: To determine whether activity of carbohydrate metabolism enzymes (aldolase, pyruvate kinase, isocitrate dehydrogenase, and malate dehydrogenase) are altered in the glaucomatous trabecular meshwork (TM) compared to controls. METHODS: Tissue specimens were obtained from trabeculectomy (n=45 open angle glaucoma; Caucasian, average age 61+/-8 years of age of both genders) and from cadaver eyes (n=15 control and n=5 glaucoma; Caucasian, average age 63+/-4 years of both genders). Protein extracts from TM tissue were prepared in a non-denaturing buffer containing 0.1% genapol. Aldolase activity was measured spectrophotometrically at 240 nm absorbance using reaction of 3-phosphoglycerate with hydrazine to form hydrazone. Pyruvate kinase activity was measured by coupling lactate dehydrogenase with NADPH and pyruvate absorbance was measured at 340 nm. Isocitrate dehydrogenase activity was measured using reduction of NADP to NADPH at the characteristic absorbance at 340 nm. Malate dehydrogenase catalyzes the interconversion of L-malate and oxaloacetate using NADP as a coenzyme, quantified by its absorbance at 340 nm. RESULTS: Aldolase, pyruvate kinase, isocitrate dehydrogenase, and malate dehyrogenase activities in the glaucomatous TM tissue were found to be reduced 70, 50, 25, and 69 percent, respectively. SDS-PAGE analysis suggests the presence of 4-hydorxynonenal (HNE) modified isocitrate dehydrogenase protein in the glaucomatous TM tissue compared to controls. CONCLUSIONS: Several Krebs cycle enzyme activities are considerably reduced in glaucomatous TM. HNE modified isocitrate dehydrogenase activity is consistent with reduced inactivated form of the protein. Lipid peroxidation product modification of aldolase, pyruvate kinase, and isocitrate dehydrogenase serves as a likely reason for the reduction of enzyme activity.

Long-term Clinical Outcomes of Pars Plana Versus Anterior Chamber Placement of Glaucoma Implant Tubes.

PURPOSE: To compare long-term surgical outcomes and complications of pars plana (PP) tube implantation with conventional anterior chamber (AC) tube implantation. MATERIALS AND METHODS: Records of patients undergoing glaucoma tube implant surgery at a single institution between 2007 and 2015 were retrospectively reviewed. Eyes were matched for glaucoma diagnosis and patient age. Demographics, baseline characteristics, and treatment outcomes were recorded. Surgical success was defined as intraocular pressure (IOP) between 6 and 21 mm Hg, no subsequent glaucoma surgeries performed, and at least light perception vision. RESULTS: Fifty-seven eyes that underwent Ahmed or Baerveldt glaucoma drainage device surgery with PP tube placement were compared with 57 eyes with AC tube placement. Mean follow-up was 43.5 months in the PP group and 35.3 months in the AC group (P=0.02). Forty-nine (86.0%) PP eyes and 46 (80.7%) AC eyes achieved surgical success (P=0.45). At last follow-up, mean IOP decreased from 29.0 to 15.1 mm Hg in the PP group (P<0.01) and from 32.7 to 15.6 mm Hg in the AC group (P<0.01). Mean number of medications decreased from 2.9 to 1.1 in the PP group (P<0.01) and from 2.8 to 1.3 in the AC group (P<0.01). Mean IOP and number of medications were similar between PP and AC groups at baseline, last follow-up, and all interim time points (P>0.05 for all). There were 16 complications in the PP group and 14 in the AC group (P=0.67). CONCLUSIONS: Long-term results of glaucoma tube implant surgery with PP versus AC implantation shows effective IOP control with similar rates of surgical success.

Comparison of silicone and polypropylene Ahmed Glaucoma Valve implants.

PURPOSE: To compare the efficacy and safety of silicone and polypropylene Ahmed Glaucoma Valves (AGVs) in patients with refractory glaucoma. METHODS: A retrospective chart review of 180 eyes of 166 patients who underwent AGV implantation with a minimum follow-up period of 3 months was performed. All patients who underwent implantation of either the AGV model S-2 (polypropylene) or model FP-7 (silicone) were included, unless previous laser cyclophotocoagulation had been performed. The primary outcome measures were the change in intraocular pressure (IOP) and visual acuity after surgery and the rate of postoperative complications. RESULTS: No significant differences were seen in the baseline characteristics of patients in each group. Baseline IOP was statistically equivalent in the 2 groups (silicone =33.8+/-11.9 mm Hg, polypropylene=33.0+/-10.3 mm Hg, P=0.6). A significant reduction in IOP from baseline was achieved after both silicone and polypropylene AGV implantation (silicone =-17.7+/-11.8 mm Hg, polypropylene =-17.7+/-11.3 mm Hg, both P<0.00005). However, there was no statistically significant difference in IOP decrease between the 2 groups at any follow-up visit (all P>0.09). The mean number of postoperative antiglaucoma medications was also similar in the silicone and the polypropylene AGV groups at each time point (all P>0.2). The rate of complications and the change in visual acuity did not differ between the 2 groups (P>0.6 and P>0.3, respectively). CONCLUSIONS: Silicone and polypropylene AGVs have similar results with respect to both safety and efficacy in the treatment of patients with refractory glaucoma.

Cataract extraction in the collaborative initial glaucoma treatment study: incidence, risk factors, and the effect of cataract progression and extraction on clinical and quality-of-life outcomes.

OBJECTIVES: To study the incidence of and predictors for cataract extraction (CE) in patients with newly diagnosed glaucoma, the impact of CE on visual function, and changes in the time around CE. METHODS: Patients were randomized to medical or surgical treatments for glaucoma at 14 centers and followed up for a median of 7.7 years. Vision-specific quality of life (VS-QOL) data were collected by telephone interview during follow-up of 607 patients randomized to medical or surgical treatments for glaucoma. The occurrence of CE was the signal event. Risk factors were evaluated using survival analyses; changes from before to after CE were evaluated by paired t tests; and trends were estimated by loess regression. RESULTS: During follow-up of 607 patients, CE took place in 99 study eyes. Initial surgery, older age, a more negative spherical equivalent, and a diagnosis of pseudoexfoliative glaucoma conferred a higher risk of CE. Visual field testing before and after CE showed the mean deviation improved but the pattern standard deviation worsened. The VS-QOL improved on most subscales. CONCLUSIONS: Initial surgery places a patient with glaucoma at a higher risk of CE. The impact of CE on visual field indexes is mixed-the mean deviation improved but the pattern standard deviation worsened. Most, but not all, VS-QOL subscales were responsive to worsening of cataract prior to and acute improvement in vision after CE.

Oculodentodigital dysplasia: new ocular findings and a novel connexin 43 mutation.

OBJECTIVES: To describe new ocular findings associated with oculodentodigital dysplasia (ODDD) and a novel mutation in the connexin 43 transmembrane domain. DESIGN: Oculodentodigital dysplasia is a rare autosomal dominant disease characterized by multiple systemic abnormalities, most commonly of the ocular, nasal, dental, and limb structures. Herein, we studied 2 patients with ODDD. We describe their clinical findings and 2 ocular abnormalities not previously emphasized or reported. RESULTS: Optic nerve and retinal dysplasia was observed in both patients, and ciliary body cysts were observed in 1 patient. Both patients carried isolated in-frame deletion and missense mutations of the GJA1 gene on chromosome 6. CONCLUSIONS: Optic nerve and retinal dysplasia had not been emphasized as ocular manifestations of ODDD. Ciliary body cysts have not previously been reported in association with ODDD. CLINICAL RELEVANCE: Our findings support the potential significance of connexin 43 in the retina, optic nerve, and ciliary body. Retinal and optic nerve dysplasia may be more common than previously appreciated and may be associated with reduced vision. In addition, the ciliary body cysts observed in 1 patient may be secondary to weakened cellular adhesions between ciliary body pigmented and nonpigmented epithelium associated with the in-frame deletion identified in the affected patient. The presence of these cysts may exacerbate glaucoma or complicate its management.

Proteomics reveal Cochlin deposits associated with glaucomatous trabecular meshwork.

The etiology of primary open angle glaucoma, a leading cause of age-related blindness, remains poorly defined, although elevated intraocular pressure (IOP) contributes to the disease progression. To better understand the mechanisms causing elevated IOP from aqueous humor circulation, we pursued proteomic analyses of trabecular meshwork (TM) from glaucoma and age-matched control donors. These analyses demonstrated that Cochlin, a protein associated with deafness disorder DFNA9, is present in glaucomatous but absent in normal TM. Cochlin was also detected in TM from the glaucomatous DBA/2J mouse preceding elevated IOP but found to be absent in three other mouse lines that do not develop elevated IOP. Histochemical analyses revealed co-deposits of Cochlin and mucopolysaccharide in human TM around Schlemm's canal, similar to that observed in the cochlea in DFNA9 deafness. Purified Cochlin was found to aggregate after sheer stress and to induce the aggregation of TM cells in vitro. Age-dependent in vivo increases in Cochlin were observed in glaucomatous TM, concomitant with a decrease in type II collagen, suggesting that Cochlin may disrupt the TM architecture and render components like collagen more susceptible to degradation and collapse. Overall, these observations suggest that Cochlin contributes to elevated IOP in primary open angle glaucoma through altered interactions within the TM extracellular matrix, resulting in cell aggregation, mucopolysaccharide deposition, and significant obstruction of the aqueous humor circulation.