Nicholas P. Bell

Risk factors for primary open angle glaucoma progression: what we know and what we need to know

Purpose of review Recent literature is reviewed in order to identify possible risk factors leading to primary open angle glaucoma progression and blindness. Recent findings Several risk factors have been suggested to be important for progression of open angle glaucoma. Intraocular pressure appears to be an important risk factor for progression of glaucoma. It is still not clear if intraocular pressure fluctuation and central corneal thickness are related to progression. Myopia might be related to glaucoma progression as well as optic disc hemorrhages. Vascular factors appear to be related to progression also. Genetics seem to play an important role in open angle glaucoma. Summary Identifying risk factors associated with progression of patients with primary open angle glaucoma is essential to our clinical practices. The level of understanding regarding those risks is suboptimal at this point. Prospective long-term studies are needed if we wish to better understand the disease and help those patients at greater risk of progression and blindness.

Risk Factors for Tube Shunt Exposure: A Matched Case-Control Study

Purpose. To evaluate potential risk factors for developing tube shunt exposure in glaucoma patients. Patients and Methods. Forty-one cases from 41 patients that had tube shunt exposure from 1996 to 2005 were identified from the Robert Cizik Eye Clinic and Bascom Palmer Eye Institute. Each case was matched with 2 controls of the same gender and with tube shunts implanted within 6 months of the index case. Conditional logistic regression was used to determine risk factors. Results. The study cohort includes a total of 121 eyes from 121 patients. The mean age was 63.6 ± 19.7 years, ranging from 1 to 96 years. The average time to exposure was 19.29 ± 23.75 months (range 0.36–85.74 months). Risk factors associated with tube exposure were Hispanic ethnicity (P = 0.0115; OR = 3.6; 95% CI, 1.3–9.7), neovascular glaucoma (P = 0.0064; OR = 28.5; 95% CI, 2.6–316.9), previous trabeculectomy (P = 0.0070; OR = 5.3; 95% CI, 1.6–17.7), and combined surgery (P = 0.0381; OR = 3.7; 95% CI, 1.1–12.7). Conclusions. Hispanic ethnicity, neovascular glaucoma, previous trabeculectomy, and combined surgery were identified as potential risk factors for tube shunt exposure. These potential risk factors should be considered when determining the indication for performing tube shunt implantation and the frequency of long-term followup.

Effects of methylprednisolone and cyclosporine A on fungal growth in vitro

PURPOSE The management of corneal transplants after mycotic keratitis often poses a therapeutic dilemma. Clinicians are hesitant to use topical steroids because of their potential enhancement of fungal growth. This study seeks to evaluate the in vitro effects of methylprednisolone and cyclosporine A on the growth of various molds that often are responsible for keratomycoses. METHODS Fusarium oxysporum, Fusarium solani, and Aspergillus fumigatus were grown in the presence of varying concentrations of methylprednisolone, cyclosporine A, and vehicle controls. Fungal growth was evaluated in a masked fashion based on the number of colonies and their morphologies. RESULTS All tested concentrations of cyclosporine A (1%, 2%, 4%) had a statistically significant suppressive effect on the growth of F. oxysporum (p<0.001) and F. solani (p<0.001) compared with methylprednisolone and vehicle control solutions. A dose-dependent decrease in the number of colonies grown also was noted for F. oxysporum (p<0.001) and F. solani (p<0.001). In the case of A. fumigatus, cyclosporine A significantly decreased the colony size (p<0.015) in a dose-dependent fashion. CONCLUSIONS Cyclosporine A appears to have an inhibitory effect on fungal growth in vitro. Cyclosporine A may be an important alternative to topical steroids for management of corneal transplants after mycotic keratitis.

Postoperative Complications in the Ahmed Baerveldt Comparison Study During Five Years of Follow-up

PURPOSE To compare the late complications in the Ahmed Baerveldt Comparison Study during 5 years of follow-up. DESIGN Multicenter, prospective randomized clinical trial. METHODS setting: Sixteen international clinical centers. STUDY POPULATION Two hundred seventy-six subjects aged 18-85 years with previous intraocular surgery or refractory glaucoma with intraocular pressure of >18 mm Hg. INTERVENTIONS Ahmed Glaucoma Valve FP7 or Baerveldt Glaucoma Implant BG 101-350. MAIN OUTCOME MEASURES Late postoperative complications (beyond 3 months), reoperations for complications, and decreased vision from complications. RESULTS Late complications developed in 56 subjects (46.8 ± 4.8 5-year cumulative % ± SE) in the Ahmed Glaucoma Valve group and 67 (56.3 ± 4.7 5-year cumulative % ± SE) in the Baerveldt Glaucoma Implant group (P = .082). The cumulative rates of serious complications were 15.9% and 24.7% in the Ahmed Glaucoma Valve and Baerveldt Glaucoma Implant groups, respectively (P = .034), although this was largely driven by subjects who had tube occlusions in the 2 groups (0.8% in the Ahmed Glaucoma Valve group and 5.7% in the Baerveldt Glaucoma Implant group, P = .037). Both groups had a relatively high incidence of persistent diplopia (12%) and corneal edema (20%), although half of the corneal edema cases were likely due to pre-existing causes other than the aqueous shunt. The incidence of tube erosion was 1% and 3% in the Ahmed Glaucoma Valve and Baerveldt Glaucoma Implant groups, respectively (P = .04). CONCLUSIONS Long-term rates of vision-threatening complications and complications resulting in reoperation were higher in the Baerveldt Glaucoma Implant than in the Ahmed Glaucoma Valve group over 5 years of follow-up.

Aqueous shunt exposure: a retrospective review of repair outcome.

PurposeTo describe the patient outcomes and factors affecting those outcomes after aqueous shunt exposure repair. Patients and MethodsForty-three eyes from Robert Cizik Eye Clinic and Bascom Palmer Eye Institute from 1995 to 2007 suffered from aqueous shunt exposure and were repaired by participating surgeons. Thirty-three were tube exposures and 7 were plate exposures. The remaining 3 exposure classified complications included a patch graft exposure, an elbow exposure, and 1 unknown complication. Forty eyes were followed for evidence of additional aqueous shunt exposures or additional surgical interventions for 46.6 weeks (40.2 wk) (range: 3 to 168 wk). ResultsSeventeen of 40 eyes required additional surgical intervention: 15 (45%) from the tube exposure group and 2 (29%) from the plate exposure group. Five (13%) eyes needed eventual removal of the shunt. Black race, diabetes mellitus, a high number of glaucoma medications before shunt implantation, a history of multiple glaucoma laser procedures, and combination of an initial aqueous shunt implantation with another surgery were found to be associated with a worse outcome after exposure repair. ConclusionsIntraocular pressure, number of medications, and visual acuity remained stable during follow-up after revision. Diabetes mellitus was associated with a shorter average time between initial repair and reintervention, and 4 other variables were associated with a higher likelihood of reintervention.

Preservative toxicity in glaucoma medication: clinical evaluation of benzalkonium chloride-free 0.5% timolol eye drops

Timolol (generic name) is a frequently used medication for the control of glaucoma. Benzalkonium chloride (BAK) is a commonly used preservative in ophthalmic solutions with a broad range of antimicrobial activity; however, this nonspecificity can result in toxicity. Adverse effects attributed to BAK, including conjunctival inflammation and fibrosis, tear film instability, corneal cytotoxicity, anterior chamber inflammation, trabecular meshwork cell apoptosis, cataract development, macular edema, and even systemic effects, have been well documented. These effects can lead to ocular discomfort, poor intraocular pressure control, glaucoma surgery failure, and decreased patient compliance. BAK use in topical medications has decreased recently as newer and less toxic preservatives have become available. Yet these preservatives still exert some toxic effects, especially in patients with chronic eye disease who use multiple drops over extended periods of time. Thus, attempts to reduce overall preservative loads for patients are important, whether it be decreasing the amount of preservative, decreasing the total number of drops patients use, or eliminating preservatives entirely. A preservative-free formulation of timolol, TIMOPTIC® in OCUDOSE®, is available in unit-dose vials. Preservative-free unit-dose vials minimize toxic adverse effects and are a good option for patients with ocular surface disease, on long-term multidrop therapy, or who simply do not tolerate the effects of preservatives due to discomfort.

Reproducibility of Scleral Spur Identification and Angle Measurements Using Fourier Domain Anterior Segment Optical Coherence Tomography

Purpose. To evaluate intraobserver and interobserver agreement in locating the scleral spur landmark (SSL) and anterior chamber angle measurements obtained using Fourier Domain Anterior Segment Optical Coherence Tomography (ASOCT) images. Methods. Two independent, masked observers (SR and AZC) identified SSLs on ASOCT images from 31 eyes with open and nonopen angles. A third independent reader, NPB, adjudicated SSL placement if identifications differed by more than 80 μm. Nine months later, SR reidentified SSLs. Intraobserver and interobserver agreement in SSL placement, trabecular-iris space area (TISA750), and angle opening distance (AOD750) were calculated. Results. In 84% of quadrants, SRs SSL placements during 2 sessions were within 80 μm in both the X- and Y-axes, and in 77% of quadrants, SR and AZC were within 80 μm in both axes. In adjudicated images, 90% of all quadrants were within 80 μm, 88% in nonopen-angle eyes, and 92% in open-angle eyes. The intraobserver and interobserver correlation coefficients (with and without adjudication) were above 0.9 for TISA750 and AOD750 for all quadrants. Conclusions. Reproducible identification of the SSL from images obtained with FD-ASOCT is possible. The ability to identify the SSL allows reproducible measurement of the anterior chamber angle using TISA750 and AOD750.

New technology for examining the anterior segment by ultrasonic biomicroscopy

PURPOSE: To compare the comfort levels and measurement accuracy of the open‐shell technique and a bag/balloon technology (ClearScan, ESI) in anterior segment ultrasound biomicroscopy. SETTING: Department of Ophthalmology and Visual Science, Robert Cizik Eye Clinic, University of Texas Medical School at Houston, Houston, Texas, USA. METHODS: In this prospective investigation, 20 subjects stated their preference and rated comfort (0 best to 5 worst) for the open‐shell technique versus the bag/balloon technology. Three anterior chamber depth and sulcus‐to‐sulcus measurements were obtained, and the mean for each structure was taken as datum for each subject. Order presentation between the 2 methods was randomized. Pairwise t tests and linear regression analysis were used to determine statistical differences. RESULTS: One hundred percent of the cohort preferred the bag/balloon technology to the traditional open‐shell technique. The mean comfort score was 0.40 ± 0.53 (SD) and 2.95 ± 0.90, respectively (P<.0001). Anterior chamber depth measurements did not differ clinically (0.056 mm) nor did sulcus‐to‐sulcus determinations (0.039 mm). CONCLUSION: Biometry, patient comfort, and ease of use were better with the ClearScan bag/balloon technology than with the traditional open‐shell technique.

Trabecular-Iris Circumference Volume in Open Angle Eyes Using Swept-Source Fourier Domain Anterior Segment Optical Coherence Tomography

Purpose. To introduce a new anterior segment optical coherence tomography parameter, trabecular-iris circumference volume (TICV), which measures the integrated volume of the peripheral angle, and establish a reference range in normal, open angle eyes. Methods. One eye of each participant with open angles and a normal anterior segment was imaged using 3D mode by the CASIA SS-1000 (Tomey, Nagoya, Japan). Trabecular-iris space area (TISA) and TICV at 500 and 750 µm were calculated. Analysis of covariance was performed to examine the effect of age and its interaction with spherical equivalent. Results. The study included 100 participants with a mean age of 50 (±15) years (range 20–79). TICV showed a normal distribution with a mean (±SD) value of 4.75 µL (±2.30) for TICV500 and a mean (±SD) value of 8.90 µL (±3.88) for TICV750. Overall, TICV showed an age-related reduction (P = 0.035). In addition, angle volume increased with increased myopia for all age groups, except for those older than 65 years. Conclusions. This study introduces a new parameter to measure peripheral angle volume, TICV, with age-adjusted normal ranges for open angle eyes. Further investigation is warranted to determine the clinical utility of this new parameter.

Optimal number of angle images for calculating anterior angle volume and iris volume measurements

PURPOSE We determined the optimal number of angle images required to obtain reliable measurements of trabecular-iris circumferential volume (TICV) and iris volume (IV) using swept-source Fourier domain anterior segment optical coherence tomography (SSFD-ASOCT) scans in narrow angle eyes. METHODS Scleral spur landmarks (SSL) were manually identified on ASOCT angle images from 128 meridians from each of 24 eyes with chronic primary angle closure (PAC) spectrum of disease. The anterior and posterior corneal curves, and the anterior and posterior iris surfaces were identified automatically by the anterior chamber analysis and interpretation (ACAI) software, then manually examined and edited by the reader if required. Trabecular-iris circumferential volume at 750 μm from SSL (TICV750) and IV were subsequently calculated using varying numbers of angle images. Threshold error was determined to be less than the lower 95% confidence limit of mean absolute percent error (MAPE) of the change in TICV or IV resulting from laser peripheral iridotomy, which would be 17% for TICV and 5% for IV, based on previous studies. The optimal number of angle images was the smallest number of images where MAPE was less than this threshold for TICV and IV. RESULTS A total of 32 equally-spaced angle images (16 meridians) was required to estimate TICV750 and 16 angle images (8 meridians) to estimate IV. Both were within 4.6% and 1.6% of MAPE, respectively. CONCLUSIONS It is possible to determine TICV and IV parameters reliably in narrow angles without evaluating all 128 meridians obtained with SSFD-ASOCT.