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.

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.

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.

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.

Concentrations of betaxolol in ocular tissues of patients with glaucoma and normal monkeys after 1 month of topical ocular administration.

PURPOSE: To measure the concentration of betaxolol in tissues of humans with glaucoma and normal monkeys after topical administration. METHODS: Enucleated eyes (n = 7) of patients with glaucoma (age range, 27-79 years), without apparent anatomic disruption that would be likely to influence betaxolol absorption and intraocular distribution (exceptions: one pseudophakic, one aphakic) or other disease, were analyzed for betaxolol concentrations after self-administration of 0.25% betaxolol twice daily for 28 days or longer. The last instillation was made within 6 hours of surgery. Cynomolgus monkeys (n = 3) received 0.25% betaxolol twice daily unilaterally for 30 days. Betaxolol was measured by HPLC and tandem mass spectrometry (MS/MS) in plasma and ocular tissues. RESULTS: In humans, mean betaxolol concentrations (excluding the aphakic patient) were 71.4 +/- 41.8 ng/g in the retina, 31.2 +/- 14.8 ng/g in the optic nerve head, and 1290 +/- 1170 ng/g in the choroid. Mean concentrations in the iris and ciliary body were 73,200 +/- 89,600 and 4,250 +/- 3,020 ng/g, respectively. Betaxolol concentration was higher in all ocular tissues than in the plasma (0.59 +/- 0.32 ng/mL). In the monkeys the concentrations in the posterior tissues of the treated eyes were higher than in the untreated eyes, with mean differences in the retina and optic nerve head of 121 and 130 ng/g, respectively. CONCLUSIONS: Topically applied betaxolol was bioavailable to posterior ocular tissues, including the retina and optic nerve head, of patients with glaucoma and of normal cynomolgus monkeys. The higher betaxolol levels in the treated versus untreated monkey eyes are consistent with betaxolol's reaching posterior tissues by local absorption and distribution.

The safety and intraocular pressure-lowering efficacy of brimonidine tartrate 0.15% preserved with polyquaternium-1.

PURPOSE: The safety and intraocular pressure (IOP)-lowering efficacy of brimonidine tartrate 0.15% preserved with polyquaternium-1 were evaluated and compared with brimonidine tartrate 0.15% preserved with chlorine dioxide in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). DESIGN: Randomized, double-masked, parallel group, multicenter equivalence study. PARTICIPANTS: Eight hundred forty-two patients randomized to the study treatments. METHODS: Patients with OAG or OHT and with qualifying IOP (22-36 mmHg at 8 am on 2 eligibility visits after an appropriate washout period from previous treatment) were assigned randomly to either brimonidine tartrate 0.15% preserved with polyquaternium-1 (brimonidine PQ) or brimonidine tartrate 0.15% preserved with chlorine dioxide (brimonidine P) dosed 3 times daily and were followed up for 6 months. Approximately one half of the study sites continued to follow up their patients for an additional 6 months to obtain longer-term safety data. RESULTS: Brimonidine PQ produced statistically significant and clinically relevant reductions from baseline ranging from 4.3 to 6.5 mmHg, which were statistically and clinically equivalent to brimonidine P at all 18 visit days and times. No safety concerns were identified based on an assessment of ocular and cardiovascular parameters. Patient discontinuations resulting from adverse events were similar for both groups and most of these were a result of signs or symptoms of ocular allergic reaction. CONCLUSIONS: Brimonidine PQ is equivalent in IOP-lowering efficacy and safety to brimonidine P.

Assessment of corneal epithelial integrity after acute exposure to ocular hypotensive agents preserved with and without benzalkonium chloride.

The corneal toxicity of 2 intraocular pressure-lowering agents was compared in a rabbit cornea model with New Zealand White rabbits. Corneal epithelial morphology and cell size were assessed by in vivo confocal microscopy. Baseline microscopic examinations were performed on 1 eye of each animal. Two weeks later, the eyes were bathed for 3 min in travoprost 0.004% preserved without benzalkonium chloride (BAK( or latanoprost 0.005% preserved with 0.02% BAK; the eyes were then rinsed with balanced salt solution, and the corneas were again examined by confocal microscopy (n=4/group). A second group of animals was exposed to the medications through a dosing regimen of 1 drop/min (lpar3 drops total) (n=4/group). In eyes treated with travoprost without BAK (3-min bath), superficial epithelial cells were similar to baseline, as indicated by their visible cell borders and bright nuclei. In contrast, the surface cells in eyes treated with latanoprost were significantly smaller and brighter and had less distinct borders. Surface cell size was significantly smaller as compared with baseline size and as compared with rabbits treated with travoprost without BAK for 3 min. Similar effects on corneal epithelial cell morphology were observed with the 1-drop/min dosing regimen. In this rabbit model, travoprost 0.004% preserved without BAK did not cause corneal epithelial toxicity; latanoprost 0.005% induced superficial cell loss, most likely caused by the presence of a relatively high concentration of BAK (0.02%).

Progression of glaucoma associated with the Sirsasana (headstand) yoga posture.

This article reports a case of progressive glaucomatous optic neuropathy and visual field loss that occurred in a patient who practiced the Sirsasana (headstand) yoga posture on a daily basis for many years. Visual field analysis was performed through standard automated perimetry. Intraocular pressure (IOP) was measured through pneumotonometry in the sitting position and in the head-down position. Stereo-optic disc photographs were obtained. IOP increased significantly in the head-down position. Optic disc evaluation revealed a new disc hemorrhage in the left eye. Visual field analysis over a period of 2 y showed progression of a superior arcuate defect in the left eye. Transient increases in IOP associated with the yoga headstand posture may lead to progressive glaucomatous optic nerve damage and visual field loss.

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.

Management of glaucoma: focus on pharmacological therapy.

Glaucoma represents a major cause of vision loss throughout the world. Primary open-angle glaucoma, the most common form of glaucoma, is a chronic, progressive disease often, though not always, accompanied by elevated intraocular pressure (IOP). In this disorder, retinal ganglion cell loss and excavation of the optic nerve head produce characteristic peripheral visual field deficits. Patients with normal-tension glaucoma present with typical visual field and optic nerve head changes, without a documented history of elevated IOP. A variety of secondary causes, such as pigment dispersion syndrome and ocular trauma, can result in glaucoma as well. Treatment of all forms of glaucoma consists of reducing IOP. With proper treatment, progression of this disease can often be delayed or prevented. Treatment options for glaucoma include medications, laser therapy and incisional surgery. Laser techniques for the reduction of IOP include argon laser trabeculoplasty and selective laser trabeculoplasty. Both techniques work by increasing outflow of aqueous humour through the trabecular meshwork. Surgical options for glaucoma treatment include trabeculectomy, glaucoma drainage tube implantation and ciliary body cyclodestruction. While each of these types of procedures is effective at lowering IOP, therapy usually begins with medications. Medications lower IOP either by reducing the production or by increasing the rate of outflow of aqueous humour within the eye. Currently, there are five major classes of drugs used for the treatment of glaucoma: (i) cholinergics (acetylcholine receptor agonists); (ii) adrenoceptor agonists; (iii) carbonic anhydrase inhibitors (CAIs); (iv) beta-adrenoceptor antagonists; and (v) prostaglandin analogues (PGAs). Treatment typically begins with the selection of an agent for IOP reduction. Although beta-adrenoceptor antagonists are still commonly used by many clinicians, the PGAs are playing an increasingly important role in the first-line therapy of glaucoma. Adjunctive agents, such as alpha-adrenoceptor agonists and CAIs are often effective at providing additional reduction in IOP for patients not controlled on monotherapy. As with any chronic disease, effective treatment depends on minimising the adverse effects of therapy and maximising patient compliance. The introduction of a variety of well tolerated and potent medications over the past few years now allows the clinician to choose a treatment regimen on an individual patient basis and thereby treat this disorder more effectively.

Effect of laser in situ keratomileusis on optic nerve head topography and retinal nerve fiber layer thickness.

PURPOSE: To determine whether laser in situ keratomileusis (LASIK) produces significant changes in optic nerve head (ONH) topography and retinal nerve fiber layer (RNFL) thickness as measured by the Heidelberg Retina Tomograph (HRT) and to evaluate the potential neuroprotective effect of topical betaxolol on these changes. SETTING: Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas, USA. METHODS: In this prospective randomized double-masked comparative case series, 34 patients having LASIK for myopia were randomly assigned to receive topical betaxolol 0.5% solution or placebo twice a day for 2 days before the procedure and 7 days after the procedure. Preoperative and postoperative (1 week and 1 and 3 months) images were made with the HRT. Four HRT parameters (rim area, rim volume, mean RNFL thickness, and cup shape measure) were analyzed in a masked fashion. The Student paired t test was used for statistical analysis. RESULTS: No significant changes from baseline occurred in any HRT parameter in either patient group or when the patients were evaluated as a single group. CONCLUSIONS: Laser in situ keratomileusis did not adversely affect ONH morphology or RNFL thickness as measured by HRT. Since no neural damage was detected, the potential neuroprotective effect of betaxolol could not be evaluated.

Travoprost--a new prostaglandin analogue for the treatment of glaucoma.

Travoprost, a highly selective and potent analogue of the prostaglandin PGF(2)(alpha), has recently been approved and marketed as a topical ocular hypotensive agent for the treatment of ocular hypertension and glaucoma. Following absorption into the eye, the free acid form of travoprost interacts with the endogenous FP prostanoid receptor to enhance aqueous humor outflow and lower intraocular pressure (IOP). Travoprost is distinguished from other marketed prostaglandin analogues in that it is a full agonist at the prostaglandin receptor. It is also highly selective with little or no affinity for other prostanoid or non-prostanoid receptors in the eye. Travoprost provides robust lowering of IOP with little diurnal fluctuation and results in low target pressures in a large percentage of patients. In controlled clinical trials, travoprost 0.004% o.d. used as monotherapy produced greater IOP reduction than timolol 0.5% b.i.d. and equal or greater reduction than latanoprost 0.005%o.d. Travoprost 0.004% was also shown to be an effective adjunctive agent offering an additional 5 - 7 mmHg IOP reduction in patients inadequately controlled on timolol 0.5%. Subgroup analysis of a large Phase III trial revealed travoprost 0.004% to be significantly more effective at lowering IOP in African American patients by almost 2 mmHg compared to non-African Americans. Moreover, a higher percentage of African American patients responded to travoprost 0.004% and reached lower target pressures than with either latanoprost 0.005% or timolol 0.5%. Travoprost is a very stable compound, maintaining its efficacy following exposure to extremely low and high temperatures, repeated freezing and thawing and exposure to light. Throughout all clinical trials, travoprost was found to be safe and well-tolerated with very few (< 5%) discontinuations due to adverse events. Travoprost 0.004% represents a clinically significant advance for the treatment of glaucoma and ocular hypertension, offering superior IOP reduction and diurnal control, especially among African American patients, in a safe, well-tolerated, stable formulation.

Comparison of the safety and efficacy of dorzolamide 2% and brimonidine 0.2% in patients with glaucoma or ocular hypertension.

PURPOSE: To compare the intraocular pressure (IOP) reduction between dorzolamide 2% and brimonidine 0.2% in primary open-angle glaucoma (POAG) or ocular hypertension (OHT). METHODS: This study was a prospective, double-masked, randomized, crossover comparison of dorzolamide 2% (Trusopt) and brimonidine 0.2% (Alphagan), three times daily during two six-week study periods. The primary endpoint was mean change from baseline in trough IOP and secondary endpoints were mean change from baseline in IOP one and three hours after dosing. T-tests and a repeated-measures ANOVA were used to statistically evaluate the data. RESULTS: Of 43 patients enrolled, 41 completed the first treatment and 38 completed both treatments. Baseline IOP for dorzolamide was 24.3 mm Hg and brimonidine, 24.6 mm Hg (P = 0.9). Mean IOP reduction at trough was similar for both agents, 3.0 mm Hg (P = 0.96). Reductions at one and three hours were comparable (P = ns). Both agents were well tolerated with adverse events consistent with the package inserts. Dorzolamide was associated with more frequent stinging (P = 0.017) and burning (P < 0.001), while brimonidine was associated with more frequent dry eye (P = 0.04). CONCLUSIONS: Dorzolamide and brimonidine, as monotherapy, produced equivalent IOP-lowering efficacy at trough and at one and three hours after instillation, and both were well tolerated.

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.

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.

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.

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.