Relationship of the 24-hour pattern of intraocular pressure with optic disc appearance in primary open-angle glaucoma.

PURPOSE: To study the relationship between the 24-hour pattern of intraocular pressure (IOP) with optic disc appearance in primary open-angle glaucoma (POAG) patients. DESIGN: Observational clinical study. PARTICIPANTS: Seventy-five eyes of 45 POAG patients. METHODS: Patients underwent 24-hour IOP assessment in a sleep laboratory. Two observers classified the optic disc appearance for each eye as either concentric or nonconcentric. The IOP measurements were obtained with the subjects in the supine and sitting positions during the diurnal period and in the supine position during the nocturnal period. The mean, peak, and trough IOP and IOP range (peak through trough) were calculated for the office-hour period (9 am to 4 pm), the diurnal period (7 am to 11 pm), the nocturnal period (11 pm to 7 am), and the 24-hour period. Further, the difference in supine and sitting IOP during the diurnal periods was calculated, and generalized estimating equations were used to compare IOP measurements in both groups. MAIN OUTCOME MEASURES: Diurnal and nocturnal IOP measurements. RESULTS: Forty eyes were classified as having concentric optic disc appearance and 35 eyes as having nonconcentric optic disc appearance. The mean nocturnal IOP was significantly greater in the concentric group (mean+/-standard deviation [SD], 24.0+/-3.8 mmHg) compared with the nonconcentric group (mean+/-SD, 21.9+/-1.9 mmHg; P = 0.004). Most IOP peaks of patients with the concentric optic disc appearance occurred during the nocturnal period, as opposed to the diurnal period of patients with the nonconcentric optic disc appearance. CONCLUSIONS: Concentric optic disc appearance may be associated with higher nocturnal IOP compared with nonconcentric optic disc appearance. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Neodymium:YAG laser anterior capsulotomy for capsular contraction syndrome.

BACKGROUND AND OBJECTIVE: This study presents the outcome of neodymium:YAG laser anterior capsulotomy for capsular contraction syndrome, the safety profile and effectiveness of which are unclear. PATIENTS AND METHODS: Records of 32 patients with a minimum of 3 months of follow-up were reviewed retrospectively. The procedure was considered successful if all of the following criteria were met: centered intraocular lens (IOL) or no obvious change in IOL centration post-capsulotomy, no evidence of re-phimosis in the follow-up period; and no further requirement for surgical intervention due to capsular contraction syndrome in the follow-up period or complications were recorded. RESULTS: The procedure was successful in 25 case; (78%). Failed cases (n = 7, 22.0%) included 5 cases of re-phimosis and 2 cases with progressive IOL decentration. The failure rate was higher in cases with preoperative IOL decentration (P< .01). CONCLUSION: Neodymium:YAG laser anterior capsulotomy was successful in the majority of cases. The failure rate was higher with preoperative IOL decentration.

Withaferin A effectively targets soluble vimentin in the glaucoma filtration surgical model of fibrosis.

Withaferin A (WFA) is a natural product that binds to soluble forms of the type III intermediate filament (IF) vimentin. Currently, it is unknown under what pathophysiological contexts vimentin is druggable, as cytoskeltal vimentin-IFs are abundantly expressed. To investigate druggability of vimentin, we exploited rabbit Tenon's capsule fibroblast (RbTCF) cell cultures and the rabbit glaucoma filtration surgical (GFS) model of fibrosis. WFA potently caused G0/G1 cell cycle inhibition (IC50 25 nM) in RbTCFs, downregulating ubiquitin E3 ligase skp2 and inducing p27(Kip1) expression. Transforming growth factor (TGF)-ß-induced myofibroblast transformation caused development of cell spheroids with numerous elongated invadopodia, which WFA blocked potently by downregulating soluble vimentin and α-smooth muscle actin (SMA) expression. In the pilot proof-of-concept study using the GFS model, subconjunctival injections of a low WFA dose reduced skp2 expression in Tenon's capsule and increased p27(Kip1) expression without significant alteration to vimentin-IFs. This treatment maintains significant nanomolar WFA concentrations in anterior segment tissues that correspond to WFA's cell cycle targeting activity. A ten-fold higher WFA dose caused potent downregulation of soluble vimentin and skp2 expression, but as found in cell cultures, no further increase in p27(Kip1) expression was observed. Instead, this high WFA dose potently induced vimentin-IF disruption and downregulated α-SMA expression that mimicked WFA activity in TGF-ß-treated RbTCFs that blocked cell contractile activity at submicromolar concentrations. These findings illuminate that localized WFA injection to ocular tissues exerts pharmacological control over the skp2-p27(Kip1) pathway by targeting of soluble vimentin in a model of surgical fibrosis.

Evaluation of extended release brimonidine intravitreal device in normotensive rabbit eyes.

PURPOSE: To evaluate the safety profile of a brimonidine extended release intravitreal implant, in normotensive rabbit eyes. METHODS: Devices were made from hollow poly-l-lactic acid (PLA) tubes and contained hundred micrograms of brimonidine pamoate. Device was injected intravitreally in one eye of 12 New Zealand pigmented rabbits, whereas other eye was injected with a sham implant in masked fashion. Ocular examination was conducted at baseline and months 1, 3 and 6 including dilated fundus examination and electro-retinogram (ERG). Four rabbits were sacrificed at each time-point for retinal histology. ERG data were compared between groups and time-points using anova. RESULTS: No complications were reported from either eye of any rabbits over a 6-month period. Photopic A wave was reduced in the control eye at 1 month compared with baseline (p < 0.01). There was no significant difference in other ERG parameters between the groups at different time-points. Gross retinal histology was normal at all time-points. CONCLUSION: Extended release intravitreal brimonidine device was found to be safe and in normotensive rabbit eyes.

Long-term results of Molteno implant insertion in cases of chronic angle closure glaucoma.

BACKGROUND: This study was undertaken to provide data on the long-term results of cases of chronic angle closure glaucoma with additional risk factors treated by Molteno implants between 1985 and 2004 at Dunedin Hospital, New Zealand. METHODS: A prospective non-comparative case series followed 21 eyes (17 patients) for a mean of 5.7 years (range 1.3-16.3 years) in terms of intraocular pressure, visual acuity and subsequent procedures. RESULTS: Insertion of a Molteno implant has controlled the intraocular pressure at 21 mmHg or less in 100% of cases at 5 years after surgery, the probability of control being 0.95 (95% CI 0.91-0.99). The mean number of hypotensive medications reduced from 2.04 (SD 0.92) preoperatively to 1.40, 0.64 and 0.66 at 1, 2 and 5 years, respectively. The mean visual acuity improved from 6/18 preoperatively to 6/12 at 1 year and declined to 6/13.5 at 2 and 5 years. CONCLUSION: Insertion of Molteno implants was a safe and effective procedure in the management of complex cases of chronic angle closure glaucoma.