Increased Risk of Glaucoma in Fuchs Endothelial Corneal Dystrophy Is Independent of TCF4 Trinucleotide Repeat Expansion.

PURPOSE: The purpose of this study was to determine the prevalence of glaucoma and/or ocular hypertension (G/OHTN) in patients with Fuchs endothelial corneal dystrophy (FECD) and correlate with FECD severity and TCF4 cytosine-thymine-guanine18.1 (CTG18.1) trinucleotide repeat expansion genotype. METHODS: We included 167 FECD probands and 110 controls from the University of Texas Southwestern Medical Center FECD Genetics Study to estimate the association between FECD and G/OHTN. Participants underwent slit-lamp microscopy for the assessment of Krachmer grade disease severity of FECD. The diagnosis of G/OHTN was ascertained using a patient-reported history of G/OHTN, previous glaucoma surgery and/or glaucoma laser procedure, and use of glaucoma drops. Genomic DNA from blood of participants was used to genotype the CTG18.1 repeat polymorphism by fragment analysis using short tandem repeat and triplet repeat primed polymerase chain reaction assays. RESULTS: We observed a 19.2% prevalence of G/OHTN in the FECD probands compared with that of 7.3% in controls. The odds ratio of developing G/OHTN in FECD cases compared with controls was estimated to be 3.34 with a 95% confidence interval of 1.42-7.79 adjusting for age and sex. Among FECD cases, the likelihood of developing G/OHTN correlated positively with Krachmer grade (P = 0.043) and age (P = 0.026). There was no statistical difference of the proportions of patients developing G/OHTN between FECD cases with and without TCF4 CTG18.1 repeat expansion (16 out of 94 and 15 out of 72, respectively, P > 0.05). CONCLUSIONS: Patients with clinically significant FECD should be routinely monitored for the development of glaucoma regardless of their TCF4 repeat expansion genotype.

Differential effects of obstructive sleep apnea on the corneal subbasal nerve plexus and retinal nerve fiber layer.

PURPOSE: Obstructive sleep apnea (OSA) is an established independent risk factor for peripheral neuropathy. Macro and microvascular changes have been documented in OSA, including high levels of potent vasoconstrictors. In diabetes, vasoconstriction has been identified as an underlying risk factor for corneal neuropathy. This study sought to establish a potential relationship between OSA and corneal nerve morphology and sensitivity, and to determine whether changes in corneal nerves may be reflective of OSA severity. DESIGN: Single center cross-sectional study. METHODS: Sixty-seven patients were stratified into two groups: those with OSA and healthy controls. Groups were matched for age, sex, race, smoking, and dry eye status. Outcome measures included serologies, a dilated fundus exam, dry eye testing, anthropometric parameters, corneal sensitivity, subbasal nerve plexus morphology, retinal nerve fiber layer (RNFL) thickness, and the use of questionnaires to assess symptoms of dry eye disease, risk of OSA, and continuous positive airway pressure (CPAP) compliance. RESULTS: No significant differences were observed in corneal nerve morphology, sensitivity, or the number of dendritic cells. In the OSA test group, RNFL thinning was noted in the superior and inferior regions of the optic disc and peripapillary region. A greater proportion of participants in the OSA group required a subsequent evaluation for glaucoma than in the control. In those with OSA, an increase in the apnea hypopnea index was associated with an increase in optic nerve cupping. CONCLUSIONS: OSA does not exert a robust effect on corneal nerves. OSA is however, associated with thinning of the RNFL. Participants with glaucomatous optic nerve changes and risk factors for OSA should be examined as uncontrolled OSA may exacerbate glaucoma progression.

Charles Bonnet Syndrome in a Patient with Parkinson's Disease and Bilateral Posterior Capsule Opacification.

Charles Bonnet syndrome (CBS) is a condition of visual hallucinations or disturbances occurring in patients with visual pathway pathology not due to underlying psychiatric, metabolic, or neurologic disease. A patient with Parkinson's disease experiencing visual hallucinations was evaluated by the ophthalmology service and found to have decreased vision due to bilateral reversible posterior capsular opacification. The patient's hallucinations did not improve on clozapine, a medication requiring careful monitoring due to potentially severe systemic side effects. However, the hallucinations resolved and vision improved after bilateral treatment of the posterior capsular opacification. Clozapine was then discontinued, and the patient was able to resume his previous Parkinson's disease therapy. This case highlights the importance of considering visual pathway pathology as a contributing factor to visual hallucinations, even in patients with previously diagnosed underlying psychiatric, metabolic, or neurologic disease that could additionally be the etiology of the visual disturbances.

Optical coherence tomography retinal nerve fiber layer analysis in eyes with long axial lengths.

PURPOSE: To evaluate the relationship between axial length (AL) and retinal nerve fiber layer (RNFL) profile and to characterize differences in optical coherence tomography RNFL of myopic glaucomatous eyes compared to nonglaucomatous eyes. METHODS: Retrospective chart review of 170 eyes of 89 subjects with optical biometry and optical coherence tomography RNFL assessment was conducted. RESULTS: Temporal RNFL thickness showed no association with AL in either glaucomatous or nonglaucomatous eyes. Nasal thinning was most strongly associated with glaucoma in myopic eyes. Both myopic glaucomatous and nonglaucomatous eyes had a mean RNFL thickness of 16-22 µm thinner than mean RNFL thickness of normal AL eyes. CONCLUSION: An average of 16-22 µm thinning of RNFL compared to nomogram can be tolerated in patients with long AL. Prominent nasal thinning likely represents changes from axial elongation. Temporal RNFL thinning in those with long AL tends to be mild, and significant thinning should raise suspicion for glaucoma.

A 10-year review of pediatric uveitis at a Hispanic-dominated tertiary pediatric ophthalmic clinic.

PURPOSE: The aim of this study was to evaluate the characteristics and outcomes of pediatric uveitis cases at a large tertiary referral center in Dallas, TX, USA. MATERIALS AND METHODS: The authors performed a retrospective chart review between 2001 and 2011 to identify children with uveitis. RESULTS: A total of 46 children (68 eyes) with uveitis were identified. Sixty-seven percent were Hispanic, and the mean age was 9.2 years. The majority of cases were idiopathic (74%). Anterior uveitis accounted for 42% of cases followed by intermediate uveitis/pars planitis (33%), posterior uveitis/retinitis (7%), and panuveitis (20%). Most patients were treated with corticosteroids (98% topical), 52% with systemic immunosuppression therapy, and 30% with surgery. Complications occurred in 74% of patients, with the most common complication being cataract development (26%), followed by posterior synechiae (24%). Twenty-four percent of patients had recurrences. Hispanic patients had worse visual acuities at presentation (P-value =0.073) and follow-up (P-value =0.057), compared to non-Hispanic patients. CONCLUSION: Pediatric uveitis cases seen in a large center in Dallas were largely idiopathic, had commonly developed complications, and were associated with worse visual outcomes in Hispanic patients.

An evidence-based review of unoprostone isopropyl ophthalmic solution 0.15% for glaucoma: place in therapy.

Glaucoma is a progressive, neurodegenerative optic nerve disease that can cause significant visual morbidity and affects over 60 million people worldwide. The only known modifiable risk factor for glaucoma at this time is elevated intraocular pressure (IOP), which may be treated with medications, laser therapy, and/or incisional surgery. Topical ocular medications are commonly used as first-line therapy for glaucoma, although side effects may limit their use. Unoprostone is a novel 22-carbon ocular hypotensive agent that may be advantageous in treating some patients with open angle glaucoma or ocular hypertension. Unlike the 20-carbon prostanoids, such as latanoprost, that lower IOP primarily through an increase in uveoscleral outflow, unoprostone may lower IOP through increased aqueous outflow via the conventional trabecular meshwork pathway. Although not as efficacious as other prostanoids, unoprostone is effective for IOP reduction both as monotherapy and adjunctive therapy with timolol. Unoprostone has decreased affinity for the prostaglandin F2α receptor, which may explain its well tolerated ocular and systemic side effect profile compared with other prostanoids.

Epidemiology and characteristics of childhood glaucoma: results from the Dallas Glaucoma Registry.

PURPOSE: Few studies have provided epidemiological characteristics of childhood glaucoma in a large, multiethnic population. This information is important if we are to better screen for and characterize this specific type of glaucoma. In this study, we evaluate the characteristics of patients with childhood glaucoma, including glaucoma suspects, as identified through the Dallas Glaucoma Registry (DGR). PATIENTS AND METHODS: The DGR catalogs the characteristics of glaucoma patients seen at University of Texas Southwestern Medical Center, an academic tertiary referral center for a large, multiethnic, urban population in the United States. We analyzed these patients with respect to race, medical and surgical treatment, cup-to-disc ratio, intraocular pressure, and visual outcomes. RESULTS: The study comprised 376 eyes of 239 childhood glaucoma patients, of whom 19% had primary congenital glaucoma, 4% had primary juvenile glaucoma, 45% had secondary glaucoma, and 31% were glaucoma suspects. Trauma and postsurgical aphakia were the most common causes for secondary glaucoma. Thirty-eight percent of patients were Hispanic, 30% were Caucasian, 21% were African American, 3% were Asian, and 9% were unknown or unreported. Male sex was more common at 56%. Of all eyes with glaucoma, 65% received surgical intervention while 70% required at least one medication for intraocular pressure control. Trabeculotomy and tube-shunt surgery were the most common surgeries performed. Of patients who could have Snellen visual acuity measured, glaucoma suspect eyes had the largest proportion of eyes (96%) with good visual acuity (better than 20/40) while primary congenital glaucoma eyes had the smallest proportion (41%) with good visual acuity. Secondary glaucoma eyes had the largest proportion of eyes (30%) with poor visual acuity (worse than count fingers). CONCLUSION: The most common etiologies of childhood glaucoma were primary congenital glaucoma and secondary causes including trauma and postsurgical aphakia. A high proportion of glaucoma patients were of Hispanic background, reflecting the patient population studied. Trabeculotomy and tube-shunt surgery were the most common surgical interventions performed.

Six-month results from a Phase III randomized trial of fixed-combination brinzolamide 1% + brimonidine 0.2% versus brinzolamide or brimonidine monotherapy in glaucoma or ocular hypertension.

BACKGROUND: The objective of this study was to examine the safety and intraocular pressure (IOP)-lowering efficacy of a fixed combination of brinzolamide 1% + brimonidine 0.2% (BBFC) after six months of treatment in patients with open-angle glaucoma or ocular hypertension. METHODS: This was a randomized, multicenter, double-masked, three-month, three-arm contribution-of-elements study with a three-month safety extension. Patients were randomly assigned 1:1:1 to treatment with BBFC, brinzolamide 1%, or brimonidine 0.2% after a washout period. Patients dosed their study medications three times daily at 8 am, 3 pm, and 10 pm for six months. Patients returned for visits at two weeks, six weeks, three months, and six months. IOP measurements were used to assess efficacy. Safety assessments were adverse events, corrected distance visual acuity, slit-lamp biomicroscopy, pachymetry, perimetry, fundus parameters, and cardiac parameters. RESULTS: A total of 690 patients were randomized. Six-month mean IOP values were similar to those at three months, when the mean IOP in patients treated with BBFC was significantly lower than that of either monotherapy group. A total of 175 patients experienced at least one treatment-related adverse event (BBFC, 33.0%; brinzolamide, 18.8%; brimonidine, 24.7%), eight of which were severe, and five resulted in discontinuation. Seventy-seven patients discontinued participation due to treatment-related adverse events (BBFC, 17.2%; brinzolamide, 2.1%; brimonidine, 14.5%). There were 21 serious adverse events (n = 7 in each group), none of which was related to treatment. Resting mean pulse and blood pressure with BBFC were similar to those with brimonidine, demonstrating modest, clinically insignificant decreases. No new or increased risks were identified with use of BBFC relative to either monotherapy. CONCLUSION: This study showed that, after six months of treatment, the safety profile of BBFC was similar to that of its individual components and its IOP-lowering activity was similar to its efficacy at three months, when it was superior to both brinzolamide 1% alone and brimonidine 0.2% alone.

Phase 3 randomized 3-month trial with an ongoing 3-month safety extension of fixed-combination brinzolamide 1%/brimonidine 0.2%.

PURPOSE: This study compared the intraocular pressure (IOP)-lowering efficacy of fixed-combination brinzolamide 1%/brimonidine 0.2% (BBFC) with that of its component medications, brinzolamide and brimonidine, in patients with open-angle glaucoma or ocular hypertension. PATIENTS AND METHODS: In this phase 3, multicenter, double-masked, parallel-group, 3-month study with a 3-month safety extension, eligible patients were randomized 1:1:1 to treatment with BBFC, brinzolamide, or brimonidine thrice daily after a washout period, during which any IOP-lowering medications were discontinued. The primary objectives of this study were to determine whether the IOP-lowering efficacy of BBFC was superior to that of brinzolamide alone and, separately, of brimonidine alone. IOP was assessed at 8:00 AM, 10:00 AM, 3:00 PM, and 5:00 PM at 2 weeks, 6 weeks, and 3 months after study drug initiation. RESULTS: A total of 690 patients were enrolled in the study, and 615 completed the 3-month visit. Baseline mean IOP levels were similar among the 3 treatment groups at each of the 4 time points assessed. At the 3-month primary endpoint, mean IOP of the BBFC group was significantly lower than that of either the brinzolamide group or the brimonidine group (P≤0.005) across all time points. At the 2- and 6-week supportive endpoints, mean IOP of the BBFC group was significantly lower at all time points than the mean IOP of either the brinzolamide group (P≤0.01) or the brimonidine group (P<0.0001). A total of 143 patients experienced at least 1 treatment-related adverse event (AE; BBFC group, n=58, 26.2%; brinzolamide group, n=44, 18.8%; brimonidine group, n=41, 17.4%), the majority of which were ocular AEs. CONCLUSIONS: This study demonstrated that BBFC has significantly superior IOP-lowering activity compared with either brinzolamide 1% or brimonidine 0.2% in patients with open-angle glaucoma or ocular hypertension while providing a safety profile which is consistent with that of the individual components.

Corneal epithelial cell viability following exposure to ophthalmic solutions containing preservatives and/or antihypertensive agents.

INTRODUCTION: This in-vitro study compared the toxicity of bimatoprost 0.01% containing benzalkonium chloride (BAK) 0.02% with other commercial BAK-free or BAK-containing prostaglandin analogs. METHODS: Six test solutions were evaluated: travoprost 0.004% with polyquaternium-1 0.001% (PQ), PQ, bimatoprost 0.01% with BAK 0.02%, latanoprost 0.005% with BAK 0.02%, tafluprost 0.0015% preservative free (PF), and BAK 0.02%. Phosphate-buffered saline (PBS) was the live control and 70% methanol was the dead control. Confluent human corneal epithelial cells were incubated with test solutions (diluted 1:5 or 1:10 with PBS) or control solutions for 10 or 25 min, after which cells were fluorescently labeled to distinguish live and dead cells. Data were expressed as a percentage of PBS live-cell fluorescence for automated readouts. Live and dead cells were manually counted for numeric analyses. RESULTS: For 1:5 and 1:10 dilutions using automated readout, cells exposed to bimatoprost with BAK, latanoprost with BAK, and BAK alone demonstrated significant reductions in the live cell signal compared with PBS, travoprost with PQ, and PQ alone (all P < 0.001). They also demonstrated significantly greater toxicity than tafluprost PF for 1:5 dilutions (all P < 0.001) and 1:10 dilutions (P ≤ 0.02), except for 1:10-diluted bimatoprost with BAK (P = 0.41). For 1:5 dilutions using manual cell count, cells exposed to bimatoprost with BAK demonstrated significant reductions in the percentage of live cells compared with PBS (P = 0.02). For 1:10 dilutions using manual cell count, cells exposed to bimatoprost with BAK, latanoprost with BAK, and BAK alone demonstrated significantly greater toxicity than PBS, travoprost with PQ, PQ alone, and tafluprost PF (all P ≤ 0.03). No significant differences were observed among PBS, travoprost with PQ, and PQ alone under any test conditions (P ≤ 0.63). CONCLUSION: This study demonstrated that BAKcontaining solutions, including bimatoprost 0.01% with BAK, were toxic to human corneal epithelial cells, whereas BAK-free solutions showed little to no evidence of toxicity.

Long-term outcomes of a pseudo 360-degree trabeculotomy ab externo technique for congenital glaucoma at children's medical center.

PURPOSE: To quantify the long-term outcomes of congenital glaucoma and surgical success rates following pseudo 360-degree trabeculotomy surgery at Children's Medical Center in Dallas. PATIENTS AND METHODS: An International Classification of Diseases (ICD-9) database was utilized for a retrospective chart review. Thirty-eight eyes of 24 who underwent primary trabeculotomy with a pseudo 360-degree technique between June 1, 1992 and December 31, 2005 were studied. RESULTS: Mean age at the time of trabeculotomy was 11.1 ± 3.0 months, with seven eyes operated on after 1 year of age. Mean follow-up was 85.1 ± 9.0 months. Mean intraocular pressure (IOP) at the time of glaucoma diagnosis was 32.7 ± 1.1 mmHg, and final mean IOP for all eyes (after trabeculotomy and any additional surgery and/or glaucoma medications) was 17.9 ± 0.8 mmHg. With trabeculotomy and medication alone, mean final IOP was 19.9 ± 1.1 mmHg, with a mean drop in IOP of 12.5 ± 1.4 mmHg. Surgical success, defined by adequate IOP control, was achieved in 30 eyes (78.96%) at most recent follow-up. Kaplan-Meier analysis demonstrated 5- and 10-year survival probabilities of 93.1% and 66.8%, respectively. Seventeen eyes (44.7% of all eyes) achieved complete success, meaning IOP control <21 mmHg without additional medical therapy. All seventeen had primary congenital glaucoma (PCG); no eyes with aphakic glaucoma (AG) or Sturge-Weber syndrome (SWS) achieved complete success. Seven eyes (18.4%) failed primary trabeculotomy. Mean time to failure was 46.9 ± 8.6 months. Eyes with SWS had a significantly higher failure rate (P = 0.009) and a 5.81 relative risk of failure (P = 0.026). CONCLUSIONS: Our long-term trabeculotomy success rates for congenital glaucoma compare favorably with existing reports in the literature. Eyes with AG and SWS may warrant consideration of alternative primary surgical methods, or closer postoperative surveillance.

Glaucoma in patients with corneal endothelial dystrophy.

OBJECTIVES: The prevalence of primary open-angle glaucoma (POAG) in patients with corneal endothelial dystrophy has not been previously studied. Prevalence of POAG in patients with endothelial dystrophy was compared with that in the general population to determine the presence of a relationship between the diseases. DESIGN: Retrospective case-control study. METHODS: A study of the prevalence of POAG in 430 eyes of 215 patients with endothelial dystrophy was conducted. Patients followed for less than 6 months were excluded. Relative risk of POAG was calculated using age- and race-matched control data from the Baltimore Eye Survey and the Los Angeles Latino Eye Survey for comparison. Ocular hypertension (OHT) and secondary glaucoma (SG) rates after penetrating keratoplasty (PK) and Descemet stripping endothelial keratoplasty (DSEK) were separately analyzed. RESULTS: Relative risk of POAG in white, African American, and Hispanic patients with endothelial dystrophy was 0.94, 2.59, and 3.7, respectively (P = 0.89, 95% confidence interval [CI], -0.028 to 0.0289; P = 0.13; 95% CI, 0.011-0.274; P = 0.055; 95% CI, 0.0423-0.356). Relative risk of SG and combined OHT/SG in PK versus DSEK was 4.15 and 1.95 (P < 0.001; 95% CI, 0.0654-0.322; P = 0.005; 95% CI, 0.116-0.332), respectively. No differences in OHT/SG rates were found comparing PK-triple with PK, DSEK-triple with DSEK, and repeat with primary PK or DSEK (P = 0.98; P = 0.62; P = 0.95; P = 0.87), respectively. CONCLUSIONS: No increased risk of POAG was found in patients with endothelial dystrophy. Increased prevalence of OHT/SG was shown with PK versus DSEK; possible mechanisms include mechanical closure of Schlemm's canal by running suture and prolonged steroid use.

Glaucoma following infantile cataract surgery.

PURPOSE: To examine incidence, risk factors, and outcomes of glaucoma following infantile cataract extraction. METHODS: A retrospective chart review of all patients who underwent cataract extraction between January 1, 1993, and December 31, 2006, at the Children's Medical Center in Dallas. RESULTS: Sixty-four eyes met inclusion criteria, of which 11 eyes (17.2%) developed glaucoma during a mean follow-up of 65.1 ± 4.3 months. Age younger than 3 months at cataract diagnosis (odds ratio 4.89, P = .05) or cataract extraction (odds ratio 4.4, P = .047) and the presence of anterior chamber anomalies (odds ratio 8.0, P = .01) were the only risk factors found to have statistical significance for the development of glaucoma. Eight of 11 eyes with glaucoma (72.2%) required at least one surgical intervention. Three of 10 eyes (30%) had a final best-corrected visual acuity below 20/400 and another 4 eyes (40%) demonstrated some degree of amblyopia. CONCLUSION: Despite modern microsurgical techniques, infantile cataract surgery continues to pose a risk of secondary glaucoma. This was particularly true when cataract was diagnosed and/or extracted in patients younger than 3 months of age. Most eyes that developed glaucoma required surgical management and visual outcomes continue to be poor in this group.

Dallas Glaucoma Registry: Preliminary Results.

BACKGROUND: Although glaucoma is a leading cause of blindness worldwide, yet there are no large databases where risk factors, current management options and outcomes may be evaluated. With this concept in mind, Dallas Glaucoma Registry was established to focus on an ethnically mixed North Texas population. METHODS: This is a retrospective, chart review of 2,484 patients (4,839 eyes) with glaucoma from three clinics. Data collected included: age, race, gender, intraocular pressure, visual acuity, central corneal thickness, cup-to-disk ratio, extent of visual field damage, glaucoma diagnoses, medical and surgical therapies. RESULTS: The most prevalent glaucoma was primary open angle glaucoma accounting for 44.4% of patients, followed by glaucoma suspect (39.5%), secondary glaucoma (7.2%), angle closure glaucoma (6.8%), normal tension glaucoma (1.7%), and childhood glaucoma (0.5%). The mean (SD) age was 68.7 (13.8) and 41.3% were non Hispanic white, 37.0% were black, 10.4% were Hispanic and 11.3% were of other ethnic origin. Hispanic representation in glaucoma did not match their numbers in general population of North Texas. CONCLUSION: Large numbers of patients in the ongoing Dallas Glaucoma Registry do provide adequate data to better understand risk factors, early detection, improved screening targets, treatment options, outcomes and future studies.

Risk factors for intraocular pressure elevation after descemet stripping automated endothelial keratoplasty.

PURPOSE: To identify the incidence of and risk factors for intraocular pressure (IOP) elevation after Descemet stripping automated endothelial keratoplasty (DSAEK). METHODS: Retrospective review was conducted of 68 consecutive DSAEK procedures alone, or in combination with phacoemulsification with intraocular lens implantation or exchange, performed by two surgeons at the University of Texas Southwestern Medical Center between 2005 and 2009. Eyes that developed IOP elevation above 21 mm Hg after DSAEK and requiring initiation or escalation of glaucoma therapy were evaluated. RESULTS: Thirty-seven (54%) eyes showed IOP elevation responsive to medical treatment by a mean follow-up of 11.38 +/- 7.81 months. Six (8.8%) eyes required glaucoma surgery. In the eyes, which developed elevated IOP, gonioscopy did not reveal any new peripheral anterior synechiae formation. Prolonged topical steroid usage, rebubbling, combined DSAEK/cataract surgery, or repeat DSAEK were not significant factors (P>0.05) for development of elevated IOP, but history of previous glaucoma or ocular hypertension (OHTN) was significant (P=0.007). CONCLUSIONS: Intraocular pressure elevation is not uncommon in eyes after DSAEK, but most cases can be controlled with conservative management. Intraocular pressure elevation post-DSAEK occurred by mechanisms other than peripheral anterior synechial angle closure. The only significant risk factor for development of elevated IOP in our series was a previous history of glaucoma or OHTN.

Ocular surface tolerability of prostaglandin analogs in patients with glaucoma or ocular hypertension.

PURPOSE: To compare the ocular surface tolerability of latanoprost 0.005% preserved with 0.02% benzalkonium chloride (BAK), bimatoprost 0.03% preserved with 0.005% BAK, and travoprost 0.004% preserved with the proprietary preservative system sofZia in patients previously treated with latanoprost. METHODS: This randomized, multicenter, investigator-masked, parallel-group study enrolled patients with open-angle glaucoma or ocular hypertension who had been on latanoprost monotherapy for at least 4 weeks. At baseline, patients were randomized to receive once-daily bimatoprost (n=35), latanoprost (n=38), or travoprost (n=33) monotherapy for 3 months. Follow-up visits were at week 1, month 1, and month 3. The primary outcome measure was physician-graded conjunctival hyperemia at month 3. Secondary outcome measures included corneal staining with fluorescein and tear breakup time (TBUT). RESULTS: There were no significant differences among the treatment groups in conjunctival hyperemia scores, corneal staining, or TBUT at the latanoprost-treated baseline or at any follow-up visit. Baseline mean (standard error of the mean) values were as follows--conjunctival hyperemia: bimatoprost 0.74 (0.10), latanoprost 0.74 (0.11), travoprost 0.86 (0.12), P=0.692; corneal staining: bimatoprost 0.59 (0.12), latanoprost 0.70 (0.13), travoprost 0.48 (0.11), P=0.423; TBUT (in seconds): bimatoprost 9.1 (1.0), latanoprost 8.6 (0.8), travoprost 7.9 (0.8), P=0.578. Month 3 values were as follows--conjunctival hyperemia: bimatoprost 0.80 (0.12), latanoprost 0.74 (0.10), travoprost 0.98 (0.13), P=0.340; corneal staining: bimatoprost 0.71 (0.78), latanoprost 0.47 (0.64), travoprost 0.36 (0.62), P=0.110; TBUT (in seconds): bimatoprost 9.7 (5.3), latanoprost 9.2 (5.3), travoprost 9.7 (6.3), P=0.909. CONCLUSIONS: There were no significant differences among bimatoprost (preserved with 0.005% BAK), latanoprost (preserved with 0.02% BAK), and travoprost (preserved with sofZia) in objective clinical measures of ocular tolerability, including physician-graded hyperemia, corneal staining, and TBUT after 3 months of treatment. Longer-term studies are needed to further evaluate the ocular surface tolerability of these prostaglandin analogs.

Aqueous humor concentrations of bimatoprost free acid, bimatoprost and travoprost free acid in cataract surgical patients administered multiple topical ocular doses of LUMIGAN or TRAVATAN.

PURPOSE: To quantify the aqueous humor (AH) concentrations of bimatoprost (amide), travoprost (isopropyl ester), and their hydrolysis products, bimatoprost free acid (BFA) and travoprost free acid (TFA), after multiple topical ocular doses of LUMIGAN and TRAVATAN, respectively, in patients awaiting cataract surgery. METHODS: In 2 separate open-label, sparse-sampling trials, glaucoma patients with cataracts received LUMIGAN (bimatoprost ophthalmic solution, 0.03%) or TRAVATAN (travoprost ophthalmic solution, 0.004%) bilaterally once daily for at least 21 days prior to cataract surgery. Anterior chamber paracentesis was performed at selected times up to 5 h after the last dose and an AH sample was collected. AH samples were assayed by an independent bioanalytical laboratory using a sensitive and validated tandem LC-MS/MS method. The assay lower limits of quantitation were 0.59 nM for bimatoprost, 0.29 nM for BFA, and 0.44 nM for TFA. RESULTS: AH concentrations of BFA (17-phenyl-trinor PGF(2alpha)) were quantifiable in all but one sample at 0.5 h. The maximum concentration achieved (C(max)) of BFA was 30.9 + or - 16.41 nM (n =5), observed at 2 h postdose. AH concentrations of bimatoprost amide were lower than BFA at all time points, with a C(max) of 6.81 + or - 1.36 nM (n = 7) at 1 h postdose. For TFA, measurable AH concentrations were obtained at all time points with a TFA C(max) of 3.91 + or - 2.27 nM (n = 5), which was observed at 3 h after the dose (all data are mean + or - SEM). CONCLUSIONS: Once daily topical ocular administration of LUMIGAN or TRAVATAN for 3 weeks resulted in significant concentrations of BFA and TFA in the AH. Quantifiable levels of bimatoprost amide were also measured. Maximum concentrations of BFA (30.9 nM) and TFA (3.91 nM) in the anterior chamber are sufficient to fully activate the FP prostanoid receptors in the target cells of the ciliary muscle and trabecular meshwork. Both bimatoprost in LUMIGAN and travoprost in TRAVATAN are essentially prodrugs that are rapidly hydrolyzed to their respective free acids that induce the IOP-lowering effect observed with both drugs in vivo.

Betaxolol hydrochloride ophthalmic suspension 0.25% and timolol gel-forming solution 0.25% and 0.5% in pediatric glaucoma: a randomized clinical trial.

PURPOSE: To describe the safety profile and clinical response on elevated intraocular pressure (IOP) of betaxolol hydrochloride ophthalmic suspension 0.25% (betaxolol) and timolol maleate ophthalmic gel-forming solution (TGFS) (0.25% and 0.5%), in subjects under 6 years of age. METHODS: Subjects were randomized to betaxolol 0.25% (twice daily) or TGFS (daily) (0.25% or 0.5%) in this double-masked study. IOPs were obtained at the same time of day (9 AM) at 2 baseline visits and weeks 2, 6, and 12. Mean change from baseline in IOP was the primary efficacy parameter. RESULTS: One hundred five subjects were randomized (34 to betaxolol, 35 to TGFS 0.25%, 36 to TGFS 0.5%). Betaxolol, TGFS 0.25%, and TGFS 0.5% produced statistically significant mean reductions in IOP; mean reductions after 12 weeks of treatment were 2.3, 2.9, and 3.7 mm Hg, respectively. In subjects who were not being treated with topical IOP-lowering medication at baseline, mean IOP reductions after 12 weeks of treatment were 3.1, 4.8, and 3.8 mm Hg, respectively. In patients discontinuing 1 or more topical IOP-lowering medications at baseline, mean IOP reductions at Week 12 were 1.8, 1.8, and 3.7 mm Hg, respectively. Responder rates (> or =15% reduction from baseline) for betaxolol, TGFS 0.25%, and TGFS 0.5% were 38.2, 45.7, and 47.2%, respectively. Adverse events were predominantly nonserious and did not interrupt patient continuation in the study. CONCLUSIONS: Betaxolol ophthalmic suspension 0.25%, TGFS 0.25%, and TGFS 0.5% were well tolerated. Despite low responder rates, all 3 treatments produced statistically significant mean reductions in IOP in pediatric glaucoma subjects.

Intraocular pressure reduction in the untreated fellow eye after selective laser trabeculoplasty.

OBJECTIVE: To investigate the effect of selective laser trabeculoplasty (SLT) on the intraocular pressure (IOP) of untreated fellow eyes in patients with open-angle glaucoma. STUDY DESIGN: Retrospective chart review. PATIENTS AND METHODS: Charts of all patients who underwent SLT at the University of Texas Southwestern Medical Center at Dallas between September 2003 and May 2006 were reviewed. Each patient had IOP measurements by Goldmann applanation tonometry in both eyes preoperatively, and at 1 hour, 2 weeks, 3 months, and 6 months postoperatively. Patient age, gender, diagnosis, central corneal thickness (CCT), previous intraocular surgeries, and degrees of laser treatment were tabulated for each patient. Patients with a history of previous glaucoma surgery in either eye were excluded as were those who underwent any change in glaucoma medications or further laser or surgical intervention in either eye within 6 months of SLT. Data were analyzed using a paired two-tailed t-test, an unpaired two-tailed t-test, ANOVA, and linear regression. RESULTS: A total of 43 patients were included through 6 months of follow-up. Mean reduction in IOP in the treated eye was 3.9 +/- 0.6 mmHg or 18.8% (p < 0.001) at final exam. Mean IOP reduction in the fellow untreated eye was 2.1 +/- 0.5 mmHg or 11.2% (p < 0.01). Patients with higher preoperative IOPs had a greater reduction in IOP in both eyes (p < 0.001 for treated eyes, and p = 0.02 for untreated eyes). Patients who were on a larger number of glaucoma medications preoperatively had a greater response in both eyes (treated eye p = 0.002, untreated eye p = 0.008). There was no significant difference in IOP response in either eye based on age, gender, CCT, degrees of treatment, or phakic status. CONCLUSIONS: SLT produces a sustained and statistically significant IOP reduction in the fellow untreated eyes of patients with open-angle glaucoma. The results of our study support a biological mechanism of action for SLT. Limitations of this study include its retrospective design, relatively small sample size, a possible effect of increased compliance with medical therapy following SLT, and an inherent bias of excluding patients who underwent a change in medications or further laser or surgical therapy during the period under review.

Corneal melting after use of nepafenac in a patient with chronic cystoid macular edema after cataract surgery.

This report describes a patient who developed a corneal melt after the use of nepafenac, a nonsteroidal antiinflammatory drug. An 82-year-old woman with chronic cystoid macular edema after cataract extraction and intraocular lens implantation in the left eye, which was clinically controlled with a topical nonsteroidal antiinflammatory drug, was initially treated with diclofenac sodium 0.1% before being treated with nepafenac 0.1%. After 5 months of nepafenac use, the patient complained of pain, a foreign body sensation, and decreased vision in her left eye. The left eye showed a peripheral corneal ulcer with no stromal cell infiltration. The corneal ulcer was scraped and cultured to show epithelial cells and neutrophils with no growth of microorganisms. The nepafenac was discontinued, and a topical antibiotic and lubrication were used. After 2 months, the patient's visual acuity improved, and she had an intact epithelium and stable corneal thinning. To the authors' knowledge, this is the first case report of a corneal melt after the prolonged use of nepafenac to treat cystoid macular edema.