The Effect of Bimatoprost Implant on Glaucoma Patients: An Observational Study.

PRCIS: In this retrospective study of glaucoma patients receiving the bimatoprost implant at Duke Eye Center, the number of topical intraocular pressure-lowering medications was significantly reduced through 12 months after the implant. PURPOSE: To study the effects of the bimatoprost implant on intraocular pressure (IOP) and the need for topical IOP-lowering medications in glaucoma patients in the clinical practice setting. PATIENTS AND METHODS: Patients who received the bimatoprost implant at Duke Eye Center from November 2020 to October 2021 were identified. Exclusion criteria included addition of other IOP-lowering medications concurrent with the implant and less than 1 month of follow-up. The change in IOP and number of topical IOP-lowering medications from baseline to months 1, 3, 6, 9, and 12 after the implant was calculated. Subgroup analysis was performed for different glaucoma severities. RESULTS: A total of 63 patients and 92 eyes were included (mean age 77.8 ± 10.1 years). Glaucoma severity ranged from mild (11%), moderate (30%), to severe (54%). There was a nonsignificant decrease in IOP at all timepoints. The mean number of topical IOP-lowering medications significantly decreased by 0.81, 0.75, 0.63, 0.70, and 0.67 at month 1, 3, 6, 9, and 12, respectively (all P < 0.001). There was no significant change in the total number of medications including the bimatoprost implant. When divided by glaucoma severity, the reduction in the number of topical medications was significant at 1, 3, and 6 months for mild/moderate disease, and at 1 month for severe disease. During the follow-up period, 19 eyes underwent additional laser or surgical procedures, 68% of which had a history of prior incisional glaucoma surgery. CONCLUSIONS: The bimatoprost implant may reduce the need for topical IOP-lowering agents over a 1-year period, especially in mild-to-moderate stage glaucoma. The efficacy of the implant may be more limited in severe glaucoma, and further work is needed to characterize its long-term effects.

Intracanalicular Dexamethasone Insert or Topical Prednisolone Following iStent and Hydrus Surgery for Glaucoma.

PRCIS: Using an intracanalicular dexamethasone insert or topical prednisolone following iStent and Hydrus surgery provided similar short-term control of postoperative inflammation. PURPOSE: The purpose of this study was to compare postoperative inflammation in patients who received an intracanalicular dexamethasone insert or topical prednisolone after iStent or Hydrus insertion during cataract surgery. PATIENTS AND METHODS: Patients receiving a dexamethasone insert after iStent or Hydrus insertion were included and compared with age-matched controls who received topical prednisolone. Preoperative data were recorded. Postoperative inflammatory cell and the proportion of patients with zero anterior chamber cells was recorded at month 1. Postoperative intraocular pressure (IOP) and rate of cystoid macular edema were recorded at months 1 and 3. RESULTS: Forty eyes receiving topical prednisolone were compared with 35 eyes receiving a dexamethasone insert after iStent or Hydrus insertion. The mean postoperative inflammatory cell for the topical group at month 1 was 0.2±0.3, and the dexamethasone group, 0.3±0.5 ( P =0.816). Overall, 70% of patients in the topical group had zero anterior chamber cell at postoperative month 1 compared with 75.8% in the dexamethasone group ( P =0.583). The mean preoperative IOP for the topical group was 18.8±5.5 and the dexamethasone group was 17.1±4.1 ( P =0.064). Mean postoperative IOP for the topical group at months 1 and 3 was 17.6±6.4 and 15.1±3.1, respectively and the dexamethasone group, 17.5±4.8 and 15.0±3.4, respectively ( P =0.772 and 0.884). One patient developed cystoid macular edema in each group. CONCLUSION: There was no statistically significant difference in the proportion of patients who had zero anterior chamber cell at postoperative month 1 between groups receiving intracanalicular dexamethasone insert or topical prednisolone.

Hydrogel Sealant for Closure of Clear Corneal Incisions in Combined Glaucoma Procedures.

Purpose: The purpose of this study is to determine whether ReSure hydrogel sealant is superior to standard suture for closure of clear corneal incisions in the setting of combined glaucoma procedures. Setting: Glaucoma Department, Duke University Eye Center. Design: This is a retrospective case series. Subjects studied were patients in a 6-year period undergoing combined phacoemulsification and glaucoma surgery. All cases were performed by the same surgeon. Wound closure methods correlated with discrete timeframes, as ReSure replaced suture midway through the study period, thereby establishing sutured closure as an analogous control group. Methods: All cases included a phacoemulsification procedure requiring a 2.4 mm clear corneal incision. Upon completion of the phacoemulsification portion of the case, the wound was closed with either ReSure hydrogel or standard 10-0 suture closure. The researchers assessed the rate of Seidel-positive corneal wound leak on postoperative day one. Results: In all cases employing ReSure, no wound leak was observed at postoperative day one. Within the suture group, 3 cases showed Seidel positivity of the corneal incision. This equates to a statistically significant difference in wound leak frequency of 2.04% (P = 0.012); confidence interval, 0.21 to 5.82. Conclusion: ReSure was able to maintain closure 100% of the time over hundreds of combined cases. Suture, though the standard of practice, did not perform to this level, presenting with 3 cases of spontaneous wound leak. We conclude that ReSure is highly effective and superior to suture in closure of clear corneal incisions in combined glaucoma procedures.

Incidence of Glaucoma Progression and Rate of Visual Field Deterioration in a Cohort of Urban Ghanaians.

PRCIS: The annual incidence of glaucoma progression (9.7%) and rates of visual field mean deviation (MD) change in progressors (-1.02±0.06 dB/y) are high in a small cohort of urban Ghanaians. PURPOSE: To report the incidence of glaucoma progression and the rate of visual field deterioration in a small cohort of Ghanaians. METHODS: One hundred ten subjects (204 eyes) diagnosed with glaucoma at a baseline population-based screening examination were re-examined a mean of 8.3±0.8 years later. Eyes were classified as having progressed if the optic disc alone, visual field alone or both showed significant glaucomatous changes on follow-up. Visual field MD was used to calculate the rate of visual field progression. RESULTS: Progression was observed in 89 (80.9%, 9.7%/year) subjects (130 eyes). Progression occurred in 32 (31.7%, 3.8%/year) subjects by optic disc alone (46 eyes), 38 (44.7%, 5.4%/year) subjects by visual field alone (58 eyes), and 19 (25.0%, 3.0%/year) subjects by both modalities (26 eyes). The average rate of change in MD differed significantly between progressors (-1.02±1.06 dB/y) and nonprogressors (+0.089±0.49 dB/y), P =0.001. The rate of visual field worsening was greater among those who were classified as having progressed by both structure and function (-1.29±0.68 dB/y) and by function alone (-1.21±1.20 dB/y) than by structure alone (-0.55±0.76 dB/y). Progression was significantly associated with older age [odds ratio (OR), 1.42; P <0.001] and higher baseline intraocular pressure (OR, 1.18; P =0.002). Factors associated with rate of MD change were baseline older age (OR, 1.66; P =0.003), higher intraocular pressure (OR, 2.81; P =0.007), better visual field MD (OR, 1.41; P =0.004), and systemic hypertension (OR, 1.15; P =0.029). CONCLUSION: The incidence and rate of visual field progression are high in this longitudinal study of Ghanaian subjects with glaucoma. The findings may have important clinical and public health policy ramifications.

Risk Factors for Corneal Striae in Eyes After Glaucoma Surgery.

PRCIS: Eyes with corneal striae had steeper cornea, induced astigmatism, and higher corneal hysteresis (CH), which implies a relationship between striae, corneal shape, and the cornea's resistance to deformation at low intraocular pressures (IOPs). BACKGROUND: Anterior corneal striae (ACS) are associated with low IOP. However, the clinical significance of ACS is unclear. Here, we aim to evaluate differences in eyes with striae compared with eyes without striae. METHODS: Adults with ACS (cases) and without ACS (controls) ≥8 weeks after glaucoma surgery with an IOP ≤10 mm Hg were enrolled. Optical coherence tomography and optical biometry were performed. CH, defined as the difference in pressure between corneal indentation and reformation in response to an air jet, was obtained by the ocular response analyzer. Hypotony maculopathy (HM) was defined as optic disc swelling, vascular tortuosity attributed to hypotony, or clinical presence of chorioretinal folds confirmed on OCT. RESULTS: One hundred sixteen eyes (76 cases, 40 controls) were included. Cases had a lower IOP compared with controls (6.5±2.3 vs. 8.5±1, P<0.0001). A 1 mm Hg increase in CH increased ACS odds [odds ratio (OR)=1.51, P=0.01]. A 1 D increase in the flattest presurgical and postsurgical corneal power increased ACS odds by 1.83 (P=0.01) and 1.41 (P=0.02), respectively. Astigmatism increased in eyes with ACS by 1.11 D (P<0.001). ACS odds were increased with every 1 minute increase in mitomycin-C duration (OR=1.58, P=0.047) and decreased with the use of topical glaucoma medication (OR=0.62, P=0.03). Visual acuity decreased from logarithm of the minimal angle of resolution 0.22 (20/33 Snellen) presurgery to 0.28 (20/38) postsurgery (P=0.008), independent of ACS. HM occurred in 19% of cases (P=0.05). A higher postsurgical CH increased HM odds (OR=1.8, P=0.003). HM predicted a 0.41 mm decrease in axial length (P<0.0001), independent of IOP. CONCLUSION: ACS were associated with a steeper cornea, induced astigmatism, and higher CH, suggesting a relationship between striae, corneal shape, and the cornea's ability to resist deformations at lower IOP. CH, HM, and axial length shortening were associated independently of IOP.

Effect of Nylon Wick Technique on Early Intraocular Pressure Control in Nonvalved Aqueous Shunt Surgery.

PRECIS: The use of nylon wicks with fenestrations in nonvalved aqueous shunt surgery significantly reduces intraocular pressure (IOP) and glaucoma medication usage in the immediate postoperative period compared with the use of fenestrations alone. PURPOSE: To compare early postoperative IOP and medication usage in patients undergoing implantation of a nonvalved aqueous shunt device with fenestrations only or fenestrations with nylon wicks. METHODS: A retrospective review of all nonvalved aqueous shunt insertions completed by one surgeon (L.W.H.) was completed using current procedure terminology. Patients undergoing Baerveldt or ClearPath 350 mm2 aqueous shunt insertion with fenestrations only (n=37) or fenestrations with 2 nylon wicks were identified (n=92). All devices were ligated with 7-0 Vicryl (polyglactin) suture, and either 4 fenestrations or 2 fenestrations and two 9-0 nylon wicks were placed anterior to the ligature. Data regarding visual acuity (VA), IOP, number of glaucoma medications, and complications were collected from the preoperative visit just before surgery, postoperative day 1, week 3 (POW3), week 5, and month 2 (POM2). The main outcome measures were VA, IOP, number of glaucoma medications, and complications at all postoperative time points. RESULTS: There was no difference in logMAR VA between the 2 groups at any time point. At POW3, IOP was significantly lower in the wick group (14.6±7.7 vs. 18.1±8.7 mm Hg, P=0.03). Number of glaucoma medications used was significantly reduced in the wick group at POW3 (0.5±0.9 vs. 1.0±1.2, P=0.02) and POM2 (0.7±1.0 vs. 1.4±1.3, P=0.02). There was no significant increase in the overall rate of complications in the wick group, but there was a higher rate of transient hyphema (28% vs. 8%, P=0.02). CONCLUSIONS: The use of 2 nylon wicks with fenestrations in nonvalved aqueous shunt device implantation can significantly lower IOP and medication burden while awaiting the dissolution of the ligature suture.

Trabecular Microbypass Stent and Phacoemulsification in African American Patients With Open-angle Glaucoma: Outcomes and Effect of Prior Laser Trabeculoplasty.

PRECIS: In African American patients with glaucoma, iStent/phacoemulsification lowered intraocular pressure and reduced glaucoma medication usage for up to 1 year, even in patients with prior selective laser trabeculoplasty (SLT). PURPOSE: Currently, no studies have examined the outcomes of a trabecular microbypass stent and phacoemulsification in African American patients. Here, the authors investigate whether iStent/phacoemulsification decreases intraocular pressure (IOP) and/or medication usage in African American patients with glaucoma. They are also interested in whether prior SLT would affect outcomes of iStent/phacoemulsification. PATIENTS AND METHODS: A multicenter, retrospective case series of eyes that underwent iStent/phacoemulsification between 2013 and 2017 with up to 1-year follow-up. Eyes with a confirmed diagnosis of glaucoma in African American patients were included. Eyes with neovascular glaucoma or closed angle glaucoma and eyes that underwent previous incisional glaucoma surgery were excluded. RESULTS: Eighty-nine eyes were included in the study and data for 66 eyes were available at postoperative year 1 (POY1). IOP decreased from 18.3±5.7 mm Hg to 15.9±4.6 (P<0.001) and glaucoma medication usage decreased from 1.9±1.1 to 1.1±1.1 (P<0.001) at POY1. Eyes that underwent prior SLT experienced less of a decrease in IOP when compared with eyes without prior SLT, but IOP at POY1 was not significantly different between these groups. Both groups had a similar reduction in medication usage. The most common complications were IOP spikes on postoperative day 1 and microhyphemas. CONCLUSIONS: In this cohort, there was a significant decrease in IOP and medication usage 1 year after iStent/phacoemulsification. iStent/phacoemulsification is an effective and safe treatment option in African American patients with glaucoma.

Open-Angle Glaucoma: Burden of Illness, Current Therapies, and the Management of Nocturnal IOP Variation.

Glaucoma is a chronic, debilitating disease and a leading cause of global blindness. Despite treatment efforts, 10% of patients demonstrate loss of vision. In the US, > 80% of glaucoma cases are classified as open-angle glaucoma (OAG), with primary open-angle (POAG) being the most common. Although there has been tremendous innovation in the surgical treatment of glaucoma as of late, two clinical variants of OAG, normal-tension glaucoma (NTG) and severe POAG, are especially challenging for providers because patients with access to care and excellent treatment options may progress despite achieving a "target" intraocular pressure value. Additionally, recent research has highlighted the importance of nocturnal IOP control in avoiding glaucomatous disease progression. There remains an unmet need for new treatment options that can effectively treat NTG and severe POAG patients, irrespective of baseline IOP, while overcoming adherence limitations of current pharmacotherapies, demonstrating a robust safety profile, and more effectively controlling nocturnal IOP.Funding The Rapid Service Fees were funded by the corresponding author, Tanner J. Ferguson, MD.

Scheduled Postoperative Ripcord Removal in Baerveldt 350 Implants: A Prospective, Randomized Trial.

PURPOSE: Many surgeons remove the ripcord in the Baerveldt glaucoma drainage device to better control tube opening and intraocular pressure (IOP) lowering postoperatively. However, complications following Baerveldt implant surgery with or without ripcord removal are not well-characterized. We performed a prospective, randomized trial to test the hypothesis that scheduled ripcord removal decreases complications and final IOP. METHODS: Eighty-one patients were enrolled and randomized to scheduled ripcord removal at postoperative week 3 or to observation. They were followed for 6 months, and outcomes were compared between the 2 groups. RESULTS: Forty-four patients were randomized to scheduled ripcord removal and 37 to observation. The intervention group had a similar rate of total complications after ripcord removal (36% vs. 24%, P=0.24), a lower rate of tube fibrin obstruction (2.3% vs. 13.5%, P=0.05), and a larger decrease in the number of medications (1.3 vs. 0.49 fewer medications, P=0.01). The removal group's mean IOP decrease was 8.6 mm Hg and success rate was 59%, defined as 5 mm Hg

Association of Long-term Ambient Black Carbon Exposure and Oxidative Stress Allelic Variants With Intraocular Pressure in Older Men.

Importance: Elevated intraocular pressure is a major risk factor for glaucoma, a leading cause of irreversible blindness worldwide. Environmental air pollution has been suggested as a potential contributor to elevated intraocular pressure; however, no studies have demonstrated such an association to date. Objective: To investigate the association of long-term ambient black carbon exposure with intraocular pressure in community-dwelling older adults. Design, Setting, and Participants: This population-based analysis, conducted from October 18, 2017, through March 22, 2018, used data from the all-male, New England-based Normative Aging Study of the US Department of Veterans Affairs. The analysis included 419 older men with a total of 911 follow-up study visits between January 1, 2000, and December 30, 2011. Intraocular pressure was measured by Goldmann applanation tonometry during the study visits. Validated spatiotemporal models were used to generate 1-year black carbon exposure levels at the addresses of the participants. Main Outcomes and Measures: An independently developed genetic score approach was used to calculate allelic risk scores for 3 pathways associated with black carbon toxicity: endothelial function, oxidative stress, and metal processing. The associations among black carbon exposure, allelic risk scores, and intraocular pressure were explored using linear mixed-effects models. Results: All 419 participants were men with a mean (SD) age of 75.3 (6.9) years. The mean (SD) 1-year black carbon exposure was 0.51 (0.18) µg/m3, and the mean (SD) intraocular pressure for the left eye was 14.1 (2.8) mm Hg and for the right eye was 14.1 (3.0) mm Hg. Of the 911 visits, 520 (57.1%) had a high endothelial function allelic risk score, 644 (70.7%) had a high metal-processing allelic risk score, and 623 (68.4%) had a high oxidative stress allelic risk score. In fully adjusted linear mixed-effects models, the association of black carbon with intraocular pressure was greater in individuals with a high oxidative stress allelic score (ß = 0.36; 95% CI, 0.003-0.73) compared with individuals with a low score (ß = -0.35; 95% CI, -0.86 to 0.15). Conclusions and Relevance: Ambient black carbon exposure may be a risk factor for increased intraocular pressure in individuals susceptible to other biological oxidative stressors. If additional studies confirm these results, monitoring ambient black carbon exposure and physiological oxidative stress may prevent the development and progression of intraocular pressure-related disease.

Eight-Year Incidence of Open-Angle Glaucoma in the Tema Eye Survey.

PURPOSE: To determine the incidence of open-angle glaucoma (OAG) and its risk factors in the Tema Eye Survey in Ghana, West Africa. DESIGN: Longitudinal, observational population-based study. PARTICIPANTS: One thousand two hundred five of 1500 participants 40 years of age or older selected randomly from 5603 participants originally drawn from the population and who had undergone a baseline examination. METHODS: All participants underwent baseline and follow-up ophthalmologic examinations 8 years apart. Glaucoma diagnosis was determined based on the International Society for Geographical and Epidemiologic Ophthalmology criteria. MAIN OUTCOME MEASURES: Incidence and odds ratio (OR). RESULTS: The response rate was 80.3%. Of 1101 nonglaucomatous participants at baseline who had complete follow-up data, 4.6% (95% confidence interval [CI], 3.7%-5.2%) demonstrated OAG over the 8-year period, or 0.58% (95% CI, 0.4%-0.8%) per year. The 8-year incidence increased with age from 3.1% in those 40 to 49 years old to 7.0% in those 60 to 69 years old. Baseline risk factors for incident OAG were male gender (OR, 2.1; 95% CI, 1.1-4.0; P = 0.025), older age relative to those 40 to 49 years old (those 50-50 years old: OR, 2.6; 95% CI, 1.2-5.7; those 60-69 years old: OR, 4.3; 95% CI, 2.0-8.8; and for those 70 years of age and older: OR, 6.3; 95% CI, 2.6-15.4; all P < 0.001), higher intraocular pressure (IOP; OR, 1.4; 95% CI, 1.1-1.8; P < 0.001), larger vertical cup-to-disc ratio (OR, 5.8; 95% CI, 5.2-6.6; P < 0.001), and thinner central cornea (OR, 1.2; 95% CI, 1.03-1.5; P = 0.013). A separate analysis performed with central corneal thickness-based IOP correction did not change the outcome of the associative model of incident glaucoma. CONCLUSIONS: The incidence of OAG is higher in this population than reported in nonblack populations outside Africa. This is important not only in Ghana and probably other West African countries but also wherever people of the West African diaspora reside. These data enhance our understanding of the epidemiologic factors of OAG in this setting and may serve as reference for public health policy and planning.

The Effect of Suture Wick Technique on Early Intraocular Pressure Control After Nonvalved (Baerveldt 350) Glaucoma Drainage Device Surgery.

PURPOSE: The purpose of this study was to compare early postoperative outcomes of patients who underwent Baerveldt 350-mm aqueous drainage device (Abbott Medical Optics Inc., Santa Ana, CA) implantation with and without 7-0 polyglactin (vicryl) suture placement through tube fenestration to serve as a stenting wick. METHODS: Patients were identified by a retrospective review of the electronic medical records of one attending surgeon's Baerveldt implantation (LWH) conducted by searching the Current Procedural Terminology code "placement of aqueous shunt." All patients had tube ligature with 7-0 vicryl suture and 6-0 prolene placed as a ripcord with 4 fenestrations. Thirty-seven patients had no vicryl wick while 38 patients had a stenting wick. Data were collected from the preoperative visit, postoperative day 1, postoperative week 3, postoperative week 5, and postoperative month 2. RESULTS: Although intraocular pressure (IOP) and number of medications were reduced at every follow-up visit, there was no significant difference in IOP, percent reduction of IOP, number of medications, and visual acuity between patients with and without vicryl wick at each time point. Both groups also had comparable morbidity with no significant difference in ripcord removal, incidence of complications, or need for additional surgery. CONCLUSIONS: Baerveldt implantation with vicryl wick placement can safely lower IOP and medication burden but does not seem to offer additional utility to fenestration without vicryl wick.

The Short-term Effect of Subtenon Sponge Application Versus Subtenon Irrigation of Mitomycin-C on the Outcomes of Trabeculectomy With Ex-PRESS Glaucoma Filtration Device: A Randomized Trial.

PURPOSE: Traditionally, during trabeculectomy, Mitomycin-C (MMC) is applied to the tissues using surgical sponges. However, alternate modes of application exist. This study assessed the success rates, complication rates, final intraocular pressure (IOP), and bleb characteristics between patients receiving subtenon MMC application by sponge versus irrigation. PATIENTS AND METHODS: A total of 100 patients with glaucoma were enrolled and each was randomized to 1 of the 2 treatment groups. Patients underwent trabeculectomy with Ex-PRESS shunt and MMC placement and were followed for 6 months. Complication rates assessed included bleb failure, bleb leaks, bleb encapsulation, and hypotony, amongst others. Additional factors evaluated included bleb morphology, glaucoma drop usage, Fluorouracil (5-FU) application, bleb revision, and subsequent glaucoma surgery. RESULTS: The irrigation method provided greater IOP lowering effects (P=0.03); correspondingly the irrigation group had higher rates of hypotony (P=0.03) but with no significant consequences. Patients who had trabeculectomy/Ex-PRESS alone had greater IOP reduction than those who had concurrent cataract surgery (P<0.001). The sponge group had higher rates of 5-FU use (P=0.007) and higher reoperation rates (P=0.02) when compared with the irrigation group. Success was defined as achieving 4 mm Hg≤IOP≤15 mm Hg without any anatomical bleb failure or subsequent glaucoma surgery. The overall success rate was 87%. CONCLUSIONS: Application of subtenon MMC by irrigation seems to provide improved short-term outcomes compared with application with sponges. With a similar safety profile, the irrigation method provides better IOP control, and decreases the need for further clinical/surgical intervention in the short-term after trabeculectomy. Longer-term studies will be useful in analyzing if these differences persist with time.

Primary Open-Angle Glaucoma Preferred Practice Pattern(®) Guidelines.

UNLABELLED: PRIMARY OPEN-ANGLE GLAUCOMA PREFERRED PRACTICE PATTERN® GUIDELINES: Evidence-based update of the Primary Open-Angle Glaucoma Preferred Practice Pattern® (PPP) guidelines, describing the diagnosis and management of patients with primary open-angle glaucoma with an algorithm for patient management and detailed recommendations for evaluation and treatment options.

Primary Angle Closure Preferred Practice Pattern(®) Guidelines.

UNLABELLED: PRIMARY ANGLE CLOSURE PREFERRED PRACTICE PATTERN® GUIDELINES: Evidence-based update of the Primary Angle Closure Preferred Practice Pattern® (PPP) guidelines, describing the diagnosis and management of patients with primary angle closure with detailed recommendations for evaluation and treatment options.

Primary Open-Angle Glaucoma Suspect Preferred Practice Pattern(®) Guidelines.

UNLABELLED: PRIMARY OPEN-ANGLE GLAUCOMA SUSPECT PREFERRED PRACTICE PATTERN® GUIDELINES: Evidence-based update of the Primary Open-Angle Suspect Glaucoma Preferred Practice Pattern® (PPP) guidelines, describing the diagnosis and management of patients with primary open-angle glaucoma suspect with detailed recommendations for evaluation and treatment options.

Mathematical Modeling of Outflow Facility Increase With Trabecular Meshwork Bypass and Schlemm Canal Dilation.

PURPOSE: To mathematically model the conventional aqueous humor outflow system with trabecular meshwork (TM) bypass and Schlemm canal (SC) dilation. METHODS: The SC was modeled as a rectangular channel with the TM modeled as a permeable membrane. The collector channels (CCs) were modeled as fluid sinks distributed along the outer wall of SC. Two different implants were investigated in this study. The Hydrus Microstent (scaffold) was modeled with a TM bypass and a dilated region in SC that was 7 or 15 mm long and approximately 5-fold larger than the normal height of SC (h0). The iStent trabecular microbypass was modeled with a similar structure except that the dilated region in SC was 1 mm long and 25% larger than h0. RESULTS: Creation of a TM bypass structure would increase the pressure in the surrounding regions inside the SC and make it close to the intraocular pressure. SC dilation would increase the pressure more uniformly in the dilated region. The pressure increase led to higher flow rates in SC and CCs, and subsequently increased outflow facility (C). If CCs were uniformly distributed, the increase in C was the smallest after implantation of 1 microbypass, compared with that after implantation of 2 microbypasses or 1 scaffold. If CCs were nonuniformly distributed, the magnitude of increase in C was sensitive to the location of implant, and the sensitivity was higher for the microbypass than the scaffold. CONCLUSION: The study showed that creation of TM bypass and SC dilation significantly increased outflow facility, and the amount of increase correlated with the length of dilated regions in SC.

Osteogenesis imperfecta and primary open angle glaucoma: genotypic analysis of a new phenotypic association.

PURPOSE: Osteogenesis imperfecta (OI) is a group of inherited disorders characterized by bone fragility. Ocular findings include blue sclera, low ocular rigidity, and thin corneal thickness. However, there are no documented cases linking OI and primary open angle glaucoma (POAG). In this report, we describe three individuals, one isolated case and two from a multiplex family, with OI type I and POAG. METHODS: Available family members with OI and POAG had a complete eye examination, including visual acuity, intraocular pressure (IOP), pachymetry, slit-lamp exam, dilated fundus exam, and visual fields. DNA from blood samples was sequenced and screened for mutations in COL1A1/2 and myocilin (MYOC). RESULTS: All subjects had OI type I. Findings of POAG included elevated IOP, normal gonioscopy, and glaucomatous optic disc cupping and visual field loss. POAG cosegregated with OI in the multiplex family. The multiplex family had a single nucleotide insertion (c.540_541insC) in COL1A1 resulting in a frameshift mutation and a premature termination codon. The sporadic case had a COL1A1 splice acceptor site mutation (c.2452-2A>T or IVS36-2A>T) predicted to result in a premature termination codon due to intron inclusion or a cryptic splice site. None of the glaucoma cases had mutations or sequence changes in MYOC. CONCLUSIONS: We identified two novel mutations in COL1A1 in individuals with OI type I and POAG. Thus, some mutations in COL1A1 may be causative for OI and POAG. Alternatively, susceptibility genes may interact with mutations in COL1A1 to cause POAG.

Investigation of known genetic risk factors for primary open angle glaucoma in two populations of African ancestry.

PURPOSE: Multiple genes have been associated with primary open angle glaucoma (POAG) in Caucasian populations. We now examine the association of these loci in populations of African ancestry, populations at particularly high risk for POAG. METHODS: We genotyped DNA samples from two populations: African American (1150 cases and 999 controls) and those from Ghana, West Africa (483 cases and 593 controls). Our analysis included 57 single nucleotide polymorphisms (SNPs) in five loci previously associated with POAG at the genome-wide level, including CDKN2B-AS1, TMCO1, CAV1/CAV2, chromosome 8q22 intergenic region, and SIX1/SIX6. We evaluated association in the full datasets, as well as subgroups with normal pressure glaucoma (NPG, maximum IOP ≤21 mm Hg) and high pressure glaucoma (HPG, IOP >21 mm Hg). RESULTS: In African Americans, we identified an association of rs10120688 in the CDNK2B-AS1 region with POAG (P = 0.0020). Several other SNPs were nominally associated, but did not survive correction for multiple testing. In the subgroup analyses, significant associations were identified for rs10965245 (P = 0.0005) in the CDKN2B-AS1 region with HPG and rs11849906 in the SIX1/SIX6 region with NPG (P = 0.006). No significant association was identified with any loci in the Ghanaian samples. CONCLUSIONS: POAG genetic susceptibility alleles associated in Caucasians appear to play a greatly reduced role in populations of African ancestry. Thus, the major genetic components of POAG of African origin remain to be identified. This finding underscores the critical need to pursue large-scale genome-wide association studies in this understudied, yet disproportionately affected population.