The Canonical Wnt Signaling Pathway Inhibits the Glucocorticoid Receptor Signaling Pathway in the Trabecular Meshwork.

Glucocorticoid-induced glaucoma is a secondary open-angle glaucoma. About 40% of the general population may develop elevated intraocular pressure on prolonged glucocorticoid treatment secondary to damages in the trabecular meshwork (TM), a tissue that regulates intraocular pressure. Therefore, identifying the key molecules responsible for glucocorticoid-induced ocular hypertension is crucial. In this study, Dickkopf-related protein 1 (Dkk1), a canonical Wnt signaling inhibitor, was found to be elevated in the aqueous humor and TM of glaucoma patients. At the signaling level, Dkk1 enhanced glucocorticoid receptor (GR) signaling, whereas Dkk1 knockdown or Wnt signaling activators decreased GR signaling in human TM cells as indicated by luciferase assays. Similarly, activation of the GR signaling inhibited Wnt signaling. At the protein level, glucocorticoid-induced extracellular matrix was inhibited by Wnt activation using Wnt activators or Dkk1 knockdown in primary human TM cells. In contrast, inhibition of canonical Wnt signaling by ß-catenin knockdown increased glucocorticoid-induced extracellular matrix proteins. At the physiological level, adenovirus-mediated Wnt3a expression decreased glucocorticoid-induced ocular hypertension in mouse eyes. In summary, Wnt and GR signaling inhibit each other in the TM, and canonical Wnt signaling activators may prevent the adverse effect of glucocorticoids in the eye.

Primary cilia signaling mediates intraocular pressure sensation.

Lowe syndrome is a rare X-linked congenital disease that presents with congenital cataracts and glaucoma, as well as renal and cerebral dysfunction. OCRL, an inositol polyphosphate 5-phosphatase, is mutated in Lowe syndrome. We previously showed that OCRL is involved in vesicular trafficking to the primary cilium. Primary cilia are sensory organelles on the surface of eukaryotic cells that mediate mechanotransduction in the kidney, brain, and bone. However, their potential role in the trabecular meshwork (TM) in the eye, which regulates intraocular pressure, is unknown. Here, we show that TM cells, which are defective in glaucoma, have primary cilia that are critical for response to pressure changes. Primary cilia in TM cells shorten in response to fluid flow and elevated hydrostatic pressure, and promote increased transcription of TNF-α, TGF-ß, and GLI1 genes. Furthermore, OCRL is found to be required for primary cilia to respond to pressure stimulation. The interaction of OCRL with transient receptor potential vanilloid 4 (TRPV4), a ciliary mechanosensory channel, suggests that OCRL may act through regulation of this channel. A novel disease-causing OCRL allele prevents TRPV4-mediated calcium signaling. In addition, TRPV4 agonist GSK 1016790A treatment reduced intraocular pressure in mice; TRPV4 knockout animals exhibited elevated intraocular pressure and shortened cilia. Thus, mechanotransduction by primary cilia in TM cells is implicated in how the eye senses pressure changes and highlights OCRL and TRPV4 as attractive therapeutic targets for the treatment of glaucoma. Implications of OCRL and TRPV4 in primary cilia function may also shed light on mechanosensation in other organ systems.

Building a Culture of Safety in Ophthalmology.

Patient safety focused on a reduction in both procedural and diagnostic error is the number one concern of the United States healthcare system in the 21st century. The American Board of Ophthalmology has a longstanding interest in patient safety, and in 2015, teamed with the American Academy of Ophthalmology to convene all ophthalmology subspecialties and other prominent national organizations to address patient safety in ophthalmology. This article reviews the topic and highlights concerns for ophthalmologists.

The Ahmed Versus Baerveldt Study: Five-Year Treatment Outcomes.

PURPOSE: To compare 2 frequently used aqueous shunts for the treatment of glaucoma. DESIGN: International, multicenter, randomized trial. PARTICIPANTS: Patients aged 18 years or older with uncontrolled glaucoma despite maximum tolerated medical therapy, many of whom had failed or were at high risk of failing trabeculectomy. METHODS: Eligible patients were randomized to receive an Ahmed-FP7 valve implant (New World Medical, Inc, Rancho Cucamonga, CA) or a Baerveldt-350 implant (Abbott Medical Optics, Inc, Santa Ana, CA) using a standardized surgical technique. MAIN OUTCOME MEASURES: The primary outcome was failure, defined as intraocular pressure (IOP) outside the target range (5-18 mmHg) or reduced <20% from baseline for 2 consecutive visits after 3 months, severe vision loss, or de novo glaucoma surgery. Secondary outcomes measures included IOP, medication use, visual acuity, complications, and interventions. RESULTS: A total of 238 patients were randomized; 124 received the Ahmed-FP7 implant, and 114 received the Baerveldt-350 implant. Baseline characteristics were similar between groups. Mean preoperative IOP was 31.4±10.8 mmHg on 3.1±1.0 glaucoma medications. At 5 years, the cumulative failure rate was 53% in the Ahmed group and 40% in the Baerveldt group (P = 0.04). The main reason for failure in both groups was high IOP, and the cumulative de novo glaucoma reoperation rate was 18% in the Ahmed group and 11% in the Baerveldt group (P = 0.22). Hypotony resulted in failure in 5 patients (4%) in the Baerveldt group compared with none in the Ahmed group (P = 0.02). Mean IOP was 16.6±5.9 mmHg in the Ahmed group (47% reduction) and 13.6±5.0 mmHg in the Baerveldt group (57% reduction, P = 0.001). Mean medication use was 1.8±1.5 mmHg in the Ahmed group (44% reduction) and 1.2±1.3 mmHg in the Baerveldt group (61% reduction, P = 0.03). The 2 groups had similar complication rates (Ahmed 63%, Baerveldt 69%) and intervention rates (Ahmed 41%, Baerveldt 41%). Most complications were transient, and most interventions were slit-lamp procedures. CONCLUSIONS: Both implants were effective in reducing IOP and the need for glaucoma medications. The Baerveldt group had a lower failure rate and a lower IOP on fewer medications than the Ahmed group, but had a small risk of hypotony that was not seen in the Ahmed group.

Integrating the Internship into Ophthalmology Residency Programs: Association of University Professors of Ophthalmology American Academy of Ophthalmology White Paper.

Future ophthalmologists will need to have broad skills to thrive in complex health care organizations. However, training for ophthalmologists does not take advantage of all of the postgraduate years (PGYs). Although the traditional residency years seem to have little excess capacity, enhancing the internship year does offer an opportunity to expand the time for ophthalmology training in the same 4 PGYs. Integrating the internship year into residency would allow control of all of the PGYs, allowing our profession to optimize training for ophthalmology. In this white paper, we propose that we could capture an additional 6 months of training time by integrating basic ophthalmology training into the intern year. This would allow 6 additional months to expand training in areas such as quality improvement or time for "mini-fellowships" to allow graduates to develop a deeper set of skills.

The Ahmed versus Baerveldt study: three-year treatment outcomes.

OBJECTIVE: To compare 2 commonly used aqueous drainage devices for the treatment of refractory glaucoma. DESIGN: International, multicenter, randomized trial. PARTICIPANTS: Patients aged 18 years or older with uncontrolled or high-risk glaucoma refractory to maximum medical therapy, many of whom had failed trabeculoplasty and trabeculectomy. METHODS: Eligible patients were randomized to an Ahmed-FP7 valve implant (New World Medical, Inc., Rancho Cucamonga, CA) or a Baerveldt-350 implant (Abbott Medical Optics, Inc., Santa Ana, CA) using a standardized surgical technique. MAIN OUTCOME MEASURES: The primary outcome was failure, defined as intraocular pressure (IOP) outside of the target range (5-18 mmHg, with ≥20% reduction from baseline) for 2 consecutive visits after 3 months, vision-threatening complications, de novo glaucoma procedures, or loss of light perception. Secondary outcome measures include IOP, medication use, visual acuity, complications, and interventions. RESULTS: A total of 238 patients were enrolled and randomized; 124 received the Ahmed implant and 114 received the Baerveldt implant. Baseline characteristics were similar in both groups. Half the study group had secondary glaucoma, and 37% had previously failed trabeculectomy. The mean preoperative IOP was 31.4±10.8 mmHg on 3.1±1.0 glaucoma medications. Median baseline Snellen visual acuity was 20/100. At 3 years, the cumulative probability of failure was 51% in the Ahmed group and 34% in the Baerveldt group (P = 0.03). Mean IOP was 15.7±4.8 mmHg in the Ahmed group (49% reduction) and 14.4±5.1 mmHg in the Baerveldt group (55% reduction; P = 0.09). Mean number of glaucoma medications was 1.8±1.4 in the Ahmed group (42% reduction) and 1.1±1.3 in the Baerveldt group (65% reduction; P = 0.002). There was a moderate but similar decrease in visual acuity in both groups (P< 0.001). The 2 groups had similar complication rates (52% Ahmed, 62% Baerveldt; P = 0.12); however, the Baerveldt group had a higher rate of hypotony-related vision-threatening complications (0% Ahmed, 6% Baerveldt; P = 0.005). More interventions were required in the Baerveldt group, although the difference did not reach statistical significance (38% Ahmed, 50% Baerveldt; P = 0.07). Most complications were transient, and most interventions were slit-lamp procedures. CONCLUSIONS: Both devices were effective in reducing IOP and glaucoma medications. The Baerveldt group had a lower failure rate and required fewer medications than the Ahmed group after 3 years, but it experienced more hypotony-related vision-threatening complications.

A narrative review on the association of high intraocular pressure and glaucoma in patients with retinal vein occlusion.

Background and Objective: Retinal vein occlusion (RVO) is a major cause of vision loss and elevated intraocular pressure (IOP), high ocular perfusion pressure, and glaucoma are known ophthalmic risk factors for RVO. The aim of this paper is to provide the update on the association and management of high IOP/glaucoma and RVO. Methods: A literature review was performed in PubMed and Medline until May 2022 utilizing specific keywords and cross-matched reference lists. Key Content and Findings: The association of RVO with high IOP/glaucoma may be attributed to retinal ganglion cell loss due to retinal ischemia in high IOP and glaucoma. As new modalities showed, decreased optic disc perfusion, reduced density of blood vessels in the optic nerve head of glaucoma patients, changes in the peripapillary microvascular parameters, and decreased retinal nerve fiber layer (RNFL) thickness of the optic nerve head of eyes with RVO suggest a common pathway between RVO and glaucoma. Literature suggests the close follow up for glaucoma development among patients with non-arteriovenous (AV) crossing (optic cup or optic nerve sited) RVO in fellow eye and management of elevated IOP among RVO cases treated with anti-vascular endothelial growth factor (VEGF) antibodies/corticosteroids and those with preexisting primary open angle glaucoma (POAG). Conclusions: Determining potential patient responses to treatment and considering therapeutic options are challenging among patients with RVO and glaucoma. However, IOP lowering managements in preventing IOP spikes in patients with preexisting glaucoma and early treatment of macular edema in eyes with RVO is recommended.

Prostaglandin-associated periorbitopathy syndrome (PAPS): Addressing an unmet clinical need.

BACKGROUND: Topical prostaglandin analogs (PGAs) are widely approved and preferred first-line options for glaucoma and elevated intraocular pressure (IOP). However, prostaglandin-associated periorbitopathy syndrome (PAPS) is now a well-recognized clinical and cosmetic concern for patients receiving PGAs, especially during long-term and unilateral therapy. PGA-associated periocular changes occur in a substantial proportion of patients, with older patients (>60 years) at greater risk of clinical presentation. PAPS may hinder long-term management of glaucoma, including treatment adherence, ophthalmic surgery outcomes, and reliable IOP measurements. RECOMMENDATION: New therapeutic approaches may address this unmet clinical need. Omidenepag isopropyl (OMDI) is a novel, non-prostaglandin, selective EP2 receptor agonist in ongoing development, which provides a unique pharmacological mechanism of action. OMDI appears to provide IOP reductions comparable to PGAs, but without PAPS-related undesirable effects. OMDI may offer a suitable long-term option for patients who demonstrate decreased efficacy, or failure, of PGAs, plus patients with significant PAPS, while fulfilling international guidelines.

The Ahmed Versus Baerveldt study: design, baseline patient characteristics, and intraoperative complications.

OBJECTIVE: To report the design, baseline patient characteristics, and intraoperative complications of the Ahmed Versus Baerveldt (AVB) Study. DESIGN: Multicenter, randomized, clinical trial. PARTICIPANTS: Patients were recruited from 7 international clinical sites and treated by 10 surgeons between 2005 and 2009. Inclusion criteria required that patients be at least 18 years of age and have uncontrolled glaucoma refractory to medicinal, laser, and surgical therapy. METHODS: Eligible patients were randomized to undergo implantation of an Ahmed-FP7 valve (New World Medical, Inc., Rancho Cucamonga, CA) or a Baerveldt-350 implant (Abbott Medical Optics, Inc., Santa Ana, CA) using standardized surgical technique, to be followed for 5 years. MAIN OUTCOME MEASURES: The primary outcome measure was failure, defined as intraocular pressure (IOP) out of target range (5-18 mmHg with ≥ 20% reduction from baseline) for 2 consecutive visits after 3 months, vision-threatening complications, additional glaucoma procedures, or loss of light perception. Secondary outcome measures included IOP, medication use, visual acuity, complications, and interventions. RESULTS: A total of 238 patients were enrolled in the study; 124 received the Ahmed-FP7 valve implant and 114 received the Baerveldt-350 implant. The 2 treatment groups did not differ in any baseline characteristics with the exception of sex. The mean age of the study group was 66 ± 16 years, and 55% were women, with a greater proportion in the Baerveldt group (P=0.01). The mean baseline IOP of the study group was 31.4 ± 10.8 on a mean of 3.1 ± 1.0 glaucoma medications. The median Snellen visual acuity was 20/100, mean number of previous laser therapies was 0.9 ± 1.1, and mean number of previous surgeries was 1.7 ± 1.2. Five (4%) patients in the Ahmed group and 4 (4%) patients in the Baerveldt group experienced significant intraoperative complications. CONCLUSIONS: Aqueous drainage devices are being increasingly used for glaucoma refractory to conventional treatment, and the AVB Study compares the 2 most commonly implanted devices. The 2 groups had similar baseline characteristics, and there were a similar number of intraoperative complications for both devices. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Update on the role of alpha-agonists in glaucoma management.

Glaucoma is the second most common cause of world blindness (following cataract) with estimated cases reaching 79.6 million by 2020. Although the etiology of glaucoma is multi-factorial, intraocular pressure (IOP) is the only modifiable factor in glaucoma management proven to alter the natural course of the disease. Among various classes of IOP-lowering medications currently available, alpha-adrenergic receptor agonists are used either as monotherapy, as second-line therapy, or in fixed combination with beta-blockers. Non-selective adrenergic agonists such as epinephrine and dipivefrin are infrequently used today for the treatment of glaucoma or ocular hypertension, and have been replaced by the alpha-2-selective agonists. The use of apraclonidine for IOP reduction in glaucoma or OHT is limited due to a high rate of follicular conjunctivitis. The alpha-2-selective agonist in use today is brimonidine. The brimonidine-purite formulations are preferred to brimonidine-benzalkonium chloride (BAC) formulations due better tolerability while maintaining similar efficacy. Brimonidine is also effective when used in combination with a beta-blocker. Using brimonidine-timolol fixed combination (BTFC) as first-line therapy has an added potential for neuroprotection. This would be a valuable strategy for glaucoma treatment, for patients who are intolerant of prostaglandin analogs, or for patients where prostaglandin analogues are contraindicated as first-line therapy, such as in patients with inflammatory glaucoma.

Cystoid macular edema related to cataract surgery and topical prostaglandin analogs: Mechanism, diagnosis, and management.

Cystoid macular edema (CME) is a form of macular retina thickening that is characterized by the appearance of cystic fluid-filled intraretinal spaces. It has classically been diagnosed upon investigation after a decrease in visual acuity; however, improvements in imaging technology make it possible to noninvasively detect CME even before a clinically significant decrease in central vision. Risk factors for the development of CME include diabetic retinopathy, retinal vein occlusion, uveitis, and cataract surgery. It has been proposed that eyes with elevated intraocular pressure after cataract surgery, including those treated with prostaglandin analog eye drops, may be at higher risk for the development of CME. We summarize the current knowledge of the molecular mechanisms underlying CME, the potential role of ocular surgery and topical glaucoma medication in increasing the risk of CME, the newly developed imaging methods for diagnosing CME, and the clinical management of CME.

Long-term outcomes of intraoperative 5-fluorouracil versus intraoperative mitomycin C in primary trabeculectomy surgery.

OBJECTIVE: To compare the long-term efficacy of intraoperative 5-fluorouracil (5-FU) and mitomycin C (MMC) in primary trabeculectomy. DESIGN: Comparative case series and extension of a prospective, randomized controlled trial. PARTICIPANTS: One hundred fifteen eyes of 103 subjects undergoing primary trabeculectomy with either intraoperative 5-FU or MMC. METHODS: This study is an extension of a 12-month, prospective, double-masked, randomized trial that previously was reported. Subjects were randomized to receive either intraoperative 5-FU (50 mg/ml for 5 minutes) or MMC (0.2 mg/ml for 2 minutes) during primary trabeculectomy. Follow-up data were collected from patient medical records after informed consent was obtained from the study patient. Attempts were made to contact subjects who had been lost to follow-up, and some consented to reexamination. MAIN OUTCOME MEASURES: The primary measure was Kaplan-Meier survival function, with failure defined as intraocular pressure (IOP) of more than 21 mmHg or less than 6 mmHg on 2 consecutive visits, less than 20% reduction from baseline IOP, loss of light perception vision, or additional glaucoma surgery to lower IOP (except bleb revision). Secondary measures included IOP, number of glaucoma medications, visual acuity, additional surgeries, and number and type of complications. RESULTS: Mean follow up was 53.4+/-31.4 months (interquartile range, 34-82 months) in the 5-FU group and 45.3+/-28.0 months (interquartile range, 19-70 months) in the MMC group (P = 0.15, t test). Kaplan-Meier success was 0.83 at 3 years and 0.76 at 5 years in the 5-FU group and 0.79 at 3 years and 0.66 at 5 years in the MMC group (P = 0.18, log-rank test). Bleb leakage was the most common complication in each group and developed in approximately 4% of subjects in each group per year (P = 0.33, log-rank test). CONCLUSIONS: There were no significant differences between topical 5-FU and topical MMC in reducing IOP of eyes undergoing primary trabeculectomy. Both antifibrosis agents may contribute to the development of bleb leakage. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Efficacy of the Ahmed S2 glaucoma valve compared with the Baerveldt 250-mm2 glaucoma implant.

OBJECTIVE: To compare the efficacy of the Ahmed S2 Glaucoma Valve with the Baerveldt 250-mm(2) Glaucoma Implant in the treatment of adult glaucoma. DESIGN: Comparative case series. PARTICIPANTS: Fifty-nine eyes of 59 patients who received the Ahmed S2 Glaucoma Valve and 133 eyes of 133 patients who received the Baerveldt 250-mm(2) Glaucoma Implant by the Indiana University Glaucoma Service from 1996 to 2003. METHODS: Eyes that had previous drainage implant procedures were excluded from both groups. If both eyes of a single patient received an implant, the second eye to undergo implantation was excluded from the study. MAIN OUTCOME MEASURES: Kaplan-Meier survival with success defined as intraocular pressure (IOP) > 5 mmHg and < 22 mmHg and at least 20% reduction from preoperative IOP (with or without antiglaucoma medications) and without loss of light perception. Secondary outcome measures included intraocular pressure, visual acuity, number of glaucoma medications, and surgical complications. RESULTS: The 2 groups were similar with regards to age, gender, race, neovascular glaucoma diagnosis, number of prior ocular surgeries, preoperative IOP, and number of preoperative glaucoma medications. Mean durations of follow-up were 20.0 months for Ahmed eyes and 22.9 months for Baerveldt eyes. Cumulative successes in the Ahmed group were 0.73 at 1 year and 0.62 at 2 years, whereas cumulative successes in the Baerveldt group were 0.92 at 1 year and 0.85 at 2 years (Kaplan-Meier survival functions: P = 0.03, log rank test). Male gender, African descent, neovascular glaucoma, and Ahmed implantation were found to be significant predictors of failure. At last follow-up visit, eyes in the Ahmed group had a significantly higher mean IOP (19.8+/-9.5 vs. 15.8+/-7.9 mmHg, P = 0.003, t test) and more antiglaucoma medications (1.4+/-1.2 vs. 0.9+/-1.1 medications, P = 0.008, Mann-Whitney test) than eyes in the Baerveldt group. Two methods for avoiding hypotony after Baerveldt 250-mm(2) implantation had similar outcomes. CONCLUSIONS: Our study suggests that the Ahmed S2 Glaucoma Valve may be less effective at lowering IOP than the Baerveldt 250-mm(2) Glaucoma Implant.

Bimatoprost/timolol fixed combination: a 3-month double-masked, randomized parallel comparison to its individual components in patients with glaucoma or ocular hypertension.

PURPOSE: To evaluate the safety and efficacy of a fixed combination (FC) of bimatoprost (BIM) and timolol (TIM) compared with each of the active components for 3 months. PATIENTS AND METHODS: Two double-masked, randomized, multicenter parallel studies of FC (once-daily, mornings), BIM (once-daily, evenings), or TIM (twice-daily) were conducted in 1061 patients with glaucoma or ocular hypertension. RESULTS: Mean diurnal decreases from baseline intraocular pressure (IOP) at month 3 were 8.1, 7.9, and 6.4 mm Hg for the FC, BIM, and TIM groups, respectively. The proportion of patients with a mean diurnal percent reduction from baseline in IOP of more than 20% across all visits was 81.8% (436/533), 72.1% (191/265), and 49.8% (131/263) for the FC, BIM, and TIM groups, respectively (P<0.001 for FC vs. BIM and FC vs. TIM). The proportion of patients achieving an IOP of less than 18 mm Hg at all time points was 39.2% (209/533), 28.7% (76/265), and 12.2% (32/263) for the FC, BIM, and TIM groups, respectively (P=0.003 for FC vs. BIM, and P<0.001 for FC vs. TIM). The most commonly reported treatment-related adverse event was conjunctival hyperemia, with the greatest incidence in BIM (38.5%, 102/265), followed by FC (22.7%, 121/533, P<0.0001 vs. BIM) and TIM (6.8%, 18/263; P<0.001 vs. FC). CONCLUSIONS: FC was statistically significantly more effective than BIM or TIM for most comparisons, and safer than BIM with respect to common ocular adverse events. FC represents a convenient, therapeutic advantage over separate bottles.

The acute and chronic effects of intravitreal anti-vascular endothelial growth factor injections on intraocular pressure: A review.

The acute and chronic effects of repeated intravitreal antivascular endothelial growth factor (VEGF) injections on intraocular pressure have not been fully characterized, and the development of sustained ocular hypertension could adversely affect patients who are at risk of glaucomatous optic neuropathy. As expected, volume-driven, acute ocular hypertension immediately follows intravitreal injection, but this pressure elevation is generally transient and well tolerated. Several medications have been investigated to limit acute ocular hypertension following anti-VEGF therapy, but the benefits of pretreatment are not conclusive. Chronic, sustained ocular hypertension, distinct from the short-term acute ocular hypertension after each injection, has also been associated with repeated intravitreal anti-VEGF injections. Risk factors for chronic ocular hypertension include the total number of injections, a greater frequency of injection, and preexisting glaucoma. Proposed mechanisms for chronic ocular hypertension include microparticle obstruction, toxic or inflammatory effects on trabecular meshwork, as well as alterations in outflow facility by anti-VEGF agents. Although limiting anti-VEGF therapy could minimize the risk of both acute and chronic ocular hypertension, foregoing anti-VEGF therapy risks progression of various macular diseases with resulting permanent central vision loss. While definitive evidence of damage to the retinal nerve fiber layer is lacking, patients receiving repeated injections should be monitored for ocular hypertension and patients in whom sustained ocular hypertension subsequently developed should be periodically monitored for glaucomatous changes with optic nerve optical coherence tomography and static visual fields.

Central corneal thickness and visual field loss in fellow eyes of patients with open-angle glaucoma.

PURPOSE: To determine the relationship of central corneal thickness (CCT) and visual field loss between fellow eyes in primary open-angle glaucoma. DESIGN: Retrospective, observational case series. METHODS: Records review of glaucoma patients seen at local Veterans Administration eye clinic. Those with CCT measurements performed within one month of visual field testing were included. Patients were excluded with vision below 20/40 or disease that would affect visual fields. Intrasubject (between fellow eyes) differences in CCT, mean deviation (MD), and pattern standard deviation (PSD) were calculated by subtracting left eye value from right eye value. RESULTS: Of the 100 subjects (94 males), the Spearman correlation coefficient between intrasubject differences in CCT vs intrasubject differences in MD was 0.36 (P = .0003). The Spearman correlation for differences in CCT vs differences in PSD was -0.31 (P = .0019). CONCLUSIONS: Our study suggests that worse visual field changes tend to occur in the eye with the thinner cornea.

Levels of bimatoprost acid in the aqueous humour after bimatoprost treatment of patients with cataract.

AIM: To determine the aqueous humour concentration of the acid hydrolysis products of bimatoprost and latanoprost after a single topical dose of bimatoprost 0.03% or latanoprost 0.005% in humans. METHODS: Randomised, controlled, double-masked, prospective study. 48 eyes of 48 patients scheduled for routine cataract surgery were randomised in an 8:2:2 ratio to treatment with a single 30 mul drop of bimatoprost 0.03%, latanoprost 0.005% or placebo at 1, 3, 6 or 12 h before the scheduled cataract surgery. Aqueous humour samples were withdrawn at the beginning of the surgical procedure and analysed using high-performance liquid chromatography-tandem mass spectrometry. RESULTS: Bimatoprost acid (17-phenyl trinor prostaglandin F2alpha) was detected in aqueous samples at a mean concentration of 5.0 nM at hour 1, 6.7 nM at hour 3 and 1.9 nM at hour 6 after bimatoprost treatment. After latanoprost treatment, the mean concentration of latanoprost acid (13,14-dihydro-17-phenyl trinor prostaglandin F2alpha) in aqueous samples was 29.1 nM at hour 1, 41.3 nM at hour 3 and 2.5 nM at hour 6. Acid metabolites were below the limit of quantitation in all samples taken 12 h after dosing and in all samples from placebo-treated patients. None of the samples from latanoprost-treated patients contained quantifiable levels of non-metabolised latanoprost. Non-metabolised bimatoprost was detected in aqueous samples at a mean concentration of 6.6 nM at hour 1 and 2.4 nM at hour 3 after bimatoprost treatment. CONCLUSIONS: Low levels of bimatoprost acid were detected in aqueous humour samples from patients with cataract treated with a single dose of bimatoprost. Latanoprost acid concentrations in samples from patients treated with latanoprost were at least sixfold higher. These results suggest that bimatoprost acid in the aqueous humour does not sufficiently account for the ocular hypotensive efficacy of bimatoprost.

Cost-comparison of two trabecular micro-bypass stents versus selective laser trabeculoplasty or medications only for intraocular pressure control for patients with open-angle glaucoma.

AIM: Patients with open-angle glaucoma (OAG) whose intraocular pressure is not adequately controlled by one medication have several treatment options in the US. This analysis evaluated direct costs of unilateral eye treatment with two trabecular micro-bypass stents (two iStents) compared to selective laser trabeculoplasty (SLT) or medications only. MATERIALS AND METHODS: A population-based, annual state-transition, probabilistic, cost-of-care model was used to assess OAG-related costs over 5 years. Patients were modeled to initiate treatment in year zero with two iStents, SLT, or medications only. In years 1-5, patients could remain on initial treatment or move to another treatment option(s), or filtration surgery. Treatment strategy change probabilities were identified by a clinician panel. Direct costs were included for drugs, procedures, and complications. RESULTS: The projected average cumulative cost at 5 years was lower in the two-stent treatment arm ($4,420) compared to the SLT arm ($4,730) or medications-only arm ($6,217). Initial year-zero costs were higher with two iStents ($2,810) than with SLT ($842) or medications only ($996). Average marginal annual costs in years 1-5 were $322 for two iStents, $777 for SLT, and $1,044 for medications only. The cumulative cost differences between two iStents vs SLT or medications only decreased over time, with breakeven by 5 or 3 years post-initiation, respectively. By year 5, cumulative savings with two iStents over SLT or medications only was $309 or $1,797, respectively. LIMITATIONS: This analysis relies on clinical expert panel opinion and would benefit from real-world evidence on use of multiple procedures and treatment switching after two-stent treatment, SLT, or polypharmaceutical initial approaches. CONCLUSIONS: Despite higher costs in year zero, annual costs thereafter were lowest in the two-stent treatment arm. Two-stent treatment may reduce OAG-related health resource use, leading to direct savings, especially over medications only or at longer time horizons.

Clinical experience with the Baerveldt 250-mm2 Glaucoma Implant.

PURPOSE: To report the intermediate-term results of the Baerveldt 250-mm2 Glaucoma Implant for treatment of adult glaucoma. DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: One hundred eight adult patients (108 eyes) with glaucoma who received a Baerveldt 250-mm2 Glaucoma Implant. INTERVENTION: Implantation of the Baerveldt 250-mm2 Glaucoma Implant. MAIN OUTCOME MEASURES: Intraocular pressure (IOP), visual acuity, number of glaucoma medications, and surgical complications. Success was defined as IOP > or = 6 mmHg and < or = 21 mmHg (with or without antiglaucoma medications), without further glaucoma surgery, devastating complication, or loss of light perception attributable to drainage implantation. RESULTS: Mean age was 63.8+/-16.5 years. Mean postoperative follow-up was 22.8 months (range, 0.2-84.9; interquartile range, 3.9-36.3). Mean preoperative IOP was 36.3+/-13.0 mmHg, on 2.9+/-1.1 antiglaucoma medications. The mean postoperative IOP at final visit was 15.8+/-7.6 mmHg (P<0.0001, paired t test), on 0.8+/-1.0 antiglaucoma medications (P<0.0001, Wilcoxon test). Kaplan-Meier success rates were 0.92 (6 months, n = 81), 0.88 (12 months, n = 75), 0.84 (18 months, n = 68), and 0.79 (24 months, n = 61). CONCLUSIONS: The Baerveldt 250-mm2 Glaucoma Implant provides good intermediate-term success for the treatment of adult refractory glaucoma.

Surgical drainage of choroidal effusions following glaucoma surgery.

PURPOSE: To determine the efficacy and safety of surgical drainage of choroidal effusions that occurs following glaucoma surgical procedures. PATIENTS AND METHODS: Ninety-four choroidal drainage procedures performed at a single institution from 1986 to 2001 were reviewed retrospectively. Sixty-three eyes of 63 persons who underwent one or more drainage procedures for choroidal effusions that developed following glaucoma surgical procedures were identified. Eyes diagnosed with suprachoroidal hemorrhage prior to intervention were excluded. The cases were evaluated for resolution of choroidal detachment, post-drainage complications, visual acuity, and intraocular pressure before and after drainage. RESULTS: Indications for choroidal drainage included flat anterior chamber (25 eyes), decreased vision (22 eyes), and persistent choroidal detachment (16 eyes). Complete resolution of choroidal effusions was achieved in 37 (59%) eyes by 1 month, 51 (81%) eyes by 2 months, and in 57 (90%) eyes by 4 months following the initial drainage procedure. Overall success rate per procedure at 12 months was 77% (60/78). Compared with pre-drainage, intraocular pressure was higher at 6 and 12 months post-drainage (P < 0.0001) and visual acuity was better at 6 and 12 months post-drainage (logMAR, P < 0.0001). Twenty-seven (77%) of 35 phakic eyes developed cataracts during the 12 months post-drainage. CONCLUSIONS: Choroidal effusions that develop after glaucoma surgery can usually be drained with minimal complications. Surgical drainage is associated with improved vision and resolution of hypotony. Cataracts may progress following choroidal drainage but this may be due to the pre-drainage hypotony conditions.