Effect of Preoperative Trabecular Meshwork Pigmentation and Other Eye Characteristics on Outcomes of Combined Phacoemulsification/Minimally Invasive Glaucoma Surgery.

PURPOSE: To investigate associations between pigmentation of the trabecular meshwork (PTM) and other preoperative eye characteristics and outcomes of minimally invasive glaucoma surgery combined with phacoemulsification (Phaco/MIGS). DESIGN: Retrospective interventional case series. PARTICIPANTS: Academic glaucoma clinic patients with symptomatic cataract and glaucoma treated with combined Phaco/MIGS. METHODS: Analyzing preoperative PTM, intraocular pressure (IOP), IOP-lowering medications and visual acuity (VA) data in relation to Phaco/MIGS outcomes. MAIN OUTCOME MEASURES: Pigmentation of the trabecular meshwork and other preoperative eye characteristics in relation to Phaco/MIGS success defined as postoperative IOP between 5 and 21 mmHg and IOP reduction of ≥ 20% and/or a reduction of ≥ 1 IOP-medications compared to baseline, and final IOP, IOP-lowering medications and VA. RESULTS: A total of 265 eyes (172 patients, mean age, 73.5 [standard deviation, 10.0], range 35-95 years, male 40.0%) were identified and categorized with high PTM (108 eyes, 40.8%) or low PTM (157 eyes, 59.2%). The high PTM group, compared with the low PTM group, demonstrated higher preoperative IOP (16.7 [standard error 0.4] vs. 15.2 [0.4] mmHg, P = 0.009), included more eyes with primary open-angle glaucoma (POAG, P = 0.03), fewer eyes with normal-tension glaucoma (NTG, P = 0.01), and fewer eyes with mild stage glaucoma (P = 0.001). Compared to baseline, final IOP decreased by 6.5 [2.4]% and 13.4 [3.0]% (P = 0.075) to 13.5 [0.3] mmHg and 13.6 [0.4] mmHg (P = 0.77) in the low and high PTM groups, respectively, and IOP-lowering medications decreased by 34.6 [4.9]% (n = 116) and 18.1 [7.3]% (n = 85), respectively (P = 0.062). Surgical success was 59.9% and 58.3%, respectively (P = 0.87). It was positively associated with higher preoperative IOP (hazard ratio 1.08 [95% confidence interval 1.04-1.12] P < 0.0001) and higher number of preoperative IOP-medications (1.20 [1.05-1.37] P = 0.007), negatively associated with history of selective laser trabeculoplasty (SLT, 0.40 [0.23-0.68] P = 0.0009) and longer axial length (0.87 [0.80-0.94], P = 0.0006), but was not associated with PTM. CONCLUSIONS: Higher PTM was associated with POAG rather than NTG, with more severe glaucoma and higher preoperative IOP, but not with Phaco/MIGS success. Surgical success was positively associated with higher preoperative IOP and number of IOP-medications and negatively associated with history of SLT and longer axial length. These findings may help guide glaucoma surgeons in surgical planning and patient counseling. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Heritable Risk and Protective Genetic Components of Glaucoma Medication Non-Adherence.

Glaucoma is the leading cause of irreversible blindness, affecting 76 million globally. It is characterized by irreversible damage to the optic nerve. Pharmacotherapy manages intraocular pressure (IOP) and slows disease progression. However, non-adherence to glaucoma medications remains problematic, with 41-71% of patients being non-adherent to their prescribed medication. Despite substantial investment in research, clinical effort, and patient education protocols, non-adherence remains high. Therefore, we aimed to determine if there is a substantive genetic component behind patients' glaucoma medication non-adherence. We assessed glaucoma medication non-adherence with prescription refill data from the Marshfield Clinic Healthcare System's pharmacy dispensing database. Two standard measures were calculated: the medication possession ratio (MPR) and the proportion of days covered (PDC). Non-adherence on each metric was defined as less than 80% medication coverage over 12 months. Genotyping was done using the Illumina HumanCoreExome BeadChip in addition to exome sequencing on the 230 patients (1) to calculate the heritability of glaucoma medication non-adherence and (2) to identify SNPs and/or coding variants in genes associated with medication non-adherence. Ingenuity pathway analysis (IPA) was utilized to derive biological meaning from any significant genes in aggregate. Over 12 months, 59% of patients were found to be non-adherent as measured by the MPR80, and 67% were non-adherent as measured by the PDC80. Genome-wide complex trait analysis (GCTA) suggested that 57% (MPR80) and 48% (PDC80) of glaucoma medication non-adherence could be attributed to a genetic component. Missense mutations in TTC28, KIAA1731, ADAMTS5, OR2W3, OR10A6, SAXO2, KCTD18, CHCHD6, and UPK1A were all found to be significantly associated with glaucoma medication non-adherence by whole exome sequencing after Bonferroni correction (p < 10-3) (PDC80). While missense mutations in TINAG, CHCHD6, GSTZ1, and SEMA4G were found to be significantly associated with medication non-adherence by whole exome sequencing after Bonferroni correction (p < 10-3) (MPR80). The same coding SNP in CHCHD6 which functions in Alzheimer's disease pathophysiology was significant by both measures and increased risk for glaucoma medication non-adherence by three-fold (95% CI, 1.62-5.8). Although our study was underpowered for genome-wide significance, SNP rs6474264 within ZMAT4 (p = 5.54 × 10-6) was found to be nominally significant, with a decreased risk for glaucoma medication non-adherence (OR, 0.22; 95% CI, 0.11-0.42)). IPA demonstrated significant overlap, utilizing, both standard measures including opioid signaling, drug metabolism, and synaptogenesis signaling. CREB signaling in neurons (which is associated with enhancing the baseline firing rate for the formation of long-term potentiation in nerve fibers) was shown to have protective associations. Our results suggest a substantial heritable genetic component to glaucoma medication non-adherence (47-58%). This finding is in line with genetic studies of other conditions with a psychiatric component (e.g., post-traumatic stress disorder (PTSD) or alcohol dependence). Our findings suggest both risk and protective statistically significant genes/pathways underlying glaucoma medication non-adherence for the first time. Further studies investigating more diverse populations with larger sample sizes are needed to validate these findings.

Survey of the American Glaucoma Society Membership on Current Glaucoma Drainage Device Placement and Postoperative Corticosteroid Use.

Purpose: To assess practice patterns and opinions of glaucoma specialists regarding glaucoma drainage device tube shunt placement and post-operative anti-inflammatory medication use. We also assess the perceived need for a randomized control trial to compare them. Patients and Methods: An online survey was distributed to a group of glaucoma specialists from the American Glaucoma Society via the American Glaucoma Society forum from April to August 2021. Results: One hundred and twenty-eight responses were included. Ninety percent placed tubes in the anterior chamber. Sixty-one percent reported that evidence suggested the superiority of sulcus tube placement over the anterior chamber, whereas 34% reported there was not enough evidence to suggest superiority of either in preventing endothelial cell loss. Comparing these techniques for intraocular pressure control, 49% reported evidence suggested sulcus tube placement superiority whereas 46% reported there was not enough evidence. Over 40% of respondents reported that they were either unfamiliar with literature or that there was not enough evidence to support the superiority of difluprednate 0.05% over prednisolone 1% for post-operative use in preventing endothelial cell loss and for intraocular pressure control. Ninety percent and 81% of respondents respectively would benefit from randomized control trials comparing outcomes of anterior chamber vs sulcus tube placement and post-operative corticosteroid usage. Conclusion: Most glaucoma specialists surveyed place glaucoma drainage device tube in the anterior chamber over the sulcus. A randomized control trial to determine optimal tube placement and post-operative anti-inflammatory medication use for preventing endothelial cell loss would change current glaucoma drainage device practice patterns.

Real-world comparison between the Tonopen and Goldmann applanation tonometry in a university glaucoma clinic.

PURPOSE: To determine whether Tonopen intraocular pressure (IOP) measurements by Ophthalmic technicians are interchangeable with Goldmann applanation tonometry (GAT) by a specialist in our glaucoma clinic. METHODS: Ophthalmic technician Tonopen and glaucoma specialist GAT IOP measurements were performed on both undilated eyes of 300 consecutive patients during the same visit to our glaucoma clinic. RESULTS: Among all 600 eyes of 300 patients (age 65.4, range: 23-92 years, male: 44.3%), Tonopen and GAT IOPs were similar (15.5 ± 0.6 vs. 15.4 ± 0.7 mmHg, respectively, p = 0.63) and directly correlated (r2 = 0.58, p < 0.0001). However, among 120 patients with bilateral primary open-angle glaucoma GAT IOP was significantly higher than Tonopen in the right eyes (17.1 ± 1.1 vs. 16.2 ± 0.9 mmHg, p = 0.024) and in the left eyes (17.0 ± 1.0 vs. 16.3 ± 1.0 mmHg, p = 0.029). In all 300 right eyes, Tonopen underestimated IOP in 48.3% of eyes and overestimated in 39% (difference range: ( - )14 to ( + )12 mmHg), with IOP difference > ± 3 mmHg in 34% of eyes. In eyes with GAT IOP ≥ 22 mmHg, Tonopen IOP was significantly lower (24.7 ± 2.6, range: 11-43 mmHg vs. 28.2 ± 2.2, range: 22-43 mmHg, p = 0.0002, mean difference: - 3.6 ± 1.7 mmHg), and the Tonopen measured IOP ≤ 21 mmHg in 33.3% of eyes. In eyes with Tonopen IOP ≤ 10 mmHg GAT measured IOP of 11-17 mmHg in 65.7% of eyes. CONCLUSIONS: Tonopen may mask a third of eyes with elevated IOP and two third of eyes with potentially above-goal IOP. The Tonopen may not be interchangeable with GAT or sufficiently reliable for patient management or screening in our glaucoma clinic. However, further study is recommended to assess the limitations of the Tonopen IOP measurements in eyes with higher or lower GAT IOPs. CLINICAL TRIALS REGISTRATION: The Institutional review board, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY does not require this retrospective study to register.

Corneal Parameters after Tube-Shunt Implantation through the Ciliary Sulcus.

PURPOSE: To monitor bilateral corneal parameters after unilateral Baerveldt 350 tube-shunt implantation (Advanced Medical Optics, Santa Ana, CA) through the ciliary sulcus. DESIGN: Retrospective, interventional case series. PARTICIPANTS: Patients from 1 private glaucoma practice with severe uncontrolled glaucoma treated with sulcus tube-shunt implantation in 1 pseudophakic eye. METHODS: Specular microscopy data were collected before and after unilateral sulcus tube-shunt implantation from the surgical and the glaucomatous fellow eyes. MAIN OUTCOME MEASURES: Central corneal endothelial cell density (CECD), coefficient of variation (CV), percent of hexagonal cells, central corneal thickness (CCT), intraocular pressure (IOP), IOP-lowering medications, visual acuity, and complications. RESULTS: Forty-six patients (mean age, 69.9 years; standard deviation [SD], 4.6 years; range, 20-88 years; male gender, 41.3%) were identified. After surgery, IOP and the number of IOP-lowering medications decreased significantly by 42.3% (P < 0.0001) and 32.1% (P < 0.0001), respectively, in the surgical eye group. Preoperative CECD measured 1807 cells/mm2 (SD, 172 cells/mm2) and 1825 cells/mm2 (SD, 172 cells/mm2) in the surgical and fellow eyes, respectively (P = 0.92), and compared with baseline, it decreased by 8.6% (P = 0.17) and 3.1% (P = 0.65), respectively, by 24 months. Preoperative CV, percent of hexagonal cells, and CCT were similar in both groups and remained stable. All corneal parameters remained unchanged in a subgroup of 15 patients with low preoperative CECD (1273 cells/mm2; SD, 99 cells/mm2). Best-corrected visual acuity remained stable in both groups. Hyphema occurred in 23.9% of the surgical eyes and resolved with no intervention. We found no sight-threatening complications or corneal failures during follow-up. CONCLUSIONS: Tube-shunt implantation through the ciliary sulcus in pseudophakic eyes appears relatively safe to the corneal endothelium, demonstrating a small and nonsignificant decline in central CECD compared with baseline and with glaucomatous fellow eyes. No significant disruption to corneal endothelial cell morphologic features, increased corneal thickness, or corneal failures were found during the 24-month follow-up period. A prospective head-to-head comparison to assess the effects of the various methods of tube-shunt implantation on the corneal endothelium is needed.

Intraocular Pressure After Cataract Surgery Combined With Ab Interno Trabeculectomy Versus Trabecular Micro-bypass Stent: An Intrasubject Same-surgeon Comparison.

PRECIS: Combining Trabectome or iStent with phacoemulsification equally reduces intraocular pressure (IOP) and IOP-lowering medication burden during a 24-month follow-up, with a possible advantage to the Trabectome in the early postoperative period. PURPOSE: Intrasubject same-surgeon comparison between phacoemulsification combined with Trabectome (Phaco/Trabectome) versus one first-generation iStent (Phaco/iStent). SETTINGS: Private glaucoma and cataract practice. DESIGN: This is a retrospective interventional case series. METHODS: Data collected at 3 to 4 and 20 to 24 hours and up to 30 months following Phaco/Trabectome in 1 eye and Phaco/iStent in the contralateral eye in patients with bilateral visually-significant cataract and open-angle glaucoma. Evaluations included IOP, intraocular pressure-lowering medications (IOPmeds), visual acuity, and complications. RESULTS: Forty-five patients (90 eyes) were identified (age 76.5, 57 to 95 y). At 3 to 4 hours, IOP was above baseline in 12 and 13 eyes following Phaco/Trabectome and Phaco/iStent, respectively, but the degree of IOP elevation was smaller (P=0.048) following Phaco/Trabectome: 4.3 mm Hg, 2.0 to 6.6 mm Hg (95% confidence interval) versus Phaco/iStent: 8.7 mm Hg, 3.8 to 13.6 mm Hg. At 20 to 24 hours, compared with baseline, IOP was significantly lower after Phaco/Trabectome (P=0.004) but not after Phaco/iStent (P=0.14) although the rate of hyphema was higher following Phaco/Trabectome (12/45 vs. 2/45 eyes, P=0.007). IOP reduction from baseline at 3 to 4 hours was significantly larger (P=0.020) in the 21 eyes with hyphema: -3.9, -6.4 to -1.4 versus the 69 eyes without hyphema: -0.3, -2.0 to +1.4. At 1, 6, 12, and 24 months, IOP and number of IOPmeds were similar and significantly lower compared with baseline following either procedure. No complications were encountered in either group. CONCLUSIONS: Combined phacoemulsification with either Trabectome or first-generation iStent similarly lowers IOP and IOPmeds burden at 1, 6, 12, and 24 months following surgery. The Trabectome may have an advantage in lowering IOP faster and lessening the degree of IOP elevations in the early postoperative period.

Two-year data comparison of ab interno trabeculectomy and trabecular bypass stenting using exact matching.

PURPOSE: To create a balanced comparison of ab interno trabeculectomy (AIT) (Trabectome) and trabecular bypass stenting (TBS) (iStent). SETTING: Eye and Ear Institute, Pittsburgh, Pennsylvania, Ross Eye Institute, Buffalo, New York, and Glaucoma Associates of Texas, Dallas, USA. DESIGN: Retrospective case series. METHODS: The primary outcome measure was an unmedicated intraocular pressure (IOP) of 21 mm Hg or less and the secondary measure was an unmedicated IOP reduction of 20% or more at 2 years. Patients were matched by baseline IOP, number of glaucoma medications, and glaucoma type using exact matching and by age using nearest neighbor matching. Individuals without a close match were excluded. All surgeries were combined with phacoemulsification. RESULTS: One hundred fifty-four AIT eyes and 110 TBS eyes were analyzed. Forty-eight AIT patients were exactly matched with 48 TBS patients. Both groups had a mean baseline IOP of 15.3 mm Hg ± 3.1 (SD). At 24 months, the mean IOP was 13.9 ± 3.3 mm Hg in AIT patients and 16.8 ± 2.8 mm Hg in TBS patients and the mean number of medications was 0.7 ± 1.0 and 1.7 ± 1.2, respectively (both P = .04). At 24 months, the IOP was 21 mm Hg or less without medications in 53% of AIT patients and 16.6% of TBS patients (P < .05). At that time, 17.6% of patients in the AIT group but no patient in the TBS group had an IOP reduction of 20% or more without medication. CONCLUSION: An exact matching comparison of AIT and TBS showed greater IOP reduction with fewer medications after AIT.

Clinical experience with urgent tube shunt implantation through the ciliary sulcus in phakic eyes.

PURPOSE: To review the clinical course and outcomes of 3 phakic, ischemic, and inflamed eyes in which we performed urgent tube shunt implantation through the ciliary sulcus without lensectomy. METHODS: This is a retrospective interventional case series. Three eyes of 3 diabetic patients with uncontrolled severe neovascular glaucoma, shallow anterior chambers with closed angles and poor view to the posterior segment, where concomitant lensectomy was not recommended due to uncontrolled uveitis and ischemia, underwent tube shunt implantation through the ciliary sulcus. Main outcome measures were surgical complications, especially injury to the crystalline lens, and postoperative intraocular pressure (IOP). RESULTS: No surgical complications, including injury to the crystalline lens, have occurred. We used surgical modifications to allow sufficient visualization of the sulcus area to avoid injury to the crystalline lens during scleral tunneling and tube insertion through the ciliary sulcus. Postoperatively, the uveitis, ischemia, and vision have improved and IOP was controlled throughout follow-up. Cataract surgery with pupilloplasty was performed in one eye a year later with no complications and no interruption to IOP control. CONCLUSIONS: Based on our small and limited retrospective study, and under unusual circumstances, urgent tube shunt implantation through the ciliary sulcus may be considered in phakic eyes with severely uncontrolled IOP, shallow anterior chambers and poor view to the posterior segment, and when concomitant lensectomy is not recommended. We advise the use of appropriate surgical modifications by experienced glaucoma surgeons to prevent intraoperative complications. Further and larger studies are needed to evaluate the safety of this surgical option.

Intraocular pressure 3 to 4 hours and 20 hours after cataract surgery with and without ab interno trabeculectomy.

PURPOSE: To evaluate intraocular pressure (IOP) immediately after cataract surgery with or without ab interno trabeculectomy (Trabectome) and whether trabeculectomy-related hyphema increases the risk for IOP spikes. SETTINGS: Private glaucoma practice. DESIGN: Retrospective interventional nonrandomized comparative chart review. METHODS: Intraocular pressure was measured 3 to 4 hours and 20 hours postoperatively. RESULTS: The combined group comprised 73 eyes of 73 patients and the cataract-only group, 75 eyes of 75 patients. The mean preoperative IOP was 15.8 mm Hg ± 3.6 (SD) and 14.9 ± 3.0 mm Hg, respectively (P = .09). In the combined group, the IOP decrease was significant at 3 to 4 hours (P = .0003) and 20 hours (P = .0007). In the cataract-only group, the IOP increased significantly (P < .0001 and P = .0035, respectively). The mean IOP was significantly lower in the combined group than in the cataract-only group at 3 to 4 hours (12.8 ± 5.9 mm Hg versus 19.7 ± 7.5 mm Hg) and 20 hours (12.7 ± 7.0 mm Hg versus 17.2 ± 5.9 mm Hg) (both P < .0001). Significantly fewer eyes in the combined group than in the cataract-only group had IOP spikes (overall, P = .0077; 3 to 4 hours, P = .001). Hyphema occurred in 35 eyes (47.9%) in the combined group; however, the IOP was similar with or without hyphema. Only 1 eye with an IOP spike in the combined group had hyphema. CONCLUSION: Combining ab interno trabeculectomy and cataract surgery reduced short-term postoperative IOP and the incidence of IOP spikes despite the common hyphema. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Clinical experience with sulcus-implanted Baerveldt glaucoma tube shunts fully concealed behind the iris in undilated pseudophakic eyes.

PURPOSE: To describe our clinical experience with ciliary sulcus-implanted Baerveldt glaucoma tube shunts entirely concealed behind the iris in undilated pseudophakic eyes (concealed tubes, CT group), compared with similarly implanted tubes whose openings remain fully exposed in the undilated pupillary area (nonconcealed tubes, NCT group). METHODS: A retrospective interventional nonrandomized comparative chart review. The main outcome measures were postoperative tube incarceration by the iris, and postoperative intraocular pressure (IOP) and the number of IOP-lowering medications. RESULTS: Fifteen eyes of 15 patients were identified in the CT group and 41 eyes of 41 patients in the NCT group. In the CT and NCT groups, the postoperative follow-up period was 14.4±10.2 months (mean±SD; range, 3 to 42 mo) and 22.9±18.1 months (mean±SD; range, 3 to 72 mo; P=0.08), respectively. Only 1 case of tube incarceration by the iris has occurred in the CT group (6.7%) and none in the NCT group. This eye was treated with laser iridotomy with no recurrence. Preoperative IOPs in the CT and the NCT groups were 27.2±9.6 mm Hg (mean±SD; range, 16 to 46 mm Hg) and 25.5±10.6 mm Hg (mean±SD; range, 12 to 59 mm Hg; P=0.6), respectively. The IOPs were significantly reduced to 13.3±4.1 mm Hg (mean±SD; range, 6 to 22 mm Hg; P=0.0001) and 10.8±4.4 mm Hg (mean±SD; range, 4 to 25 mm Hg; P=0.0001), respectively, at the final visit. The difference in the final visit IOP between the groups approached significance (P=0.056). The number of preoperative IOP-lowering medications was 3.9±0.7 (mean±SD; range, 2 to 5) and 4.0±1.0 (mean±SD; range, 1 to 6), respectively. It was significantly reduced to 1.9±1.2 (mean±SD; range, 0 to 4; P=0.0001) and 1.8±1.4 (mean±SD; range, 0 to 5; P=0.0001), respectively. There was no significant difference between the groups before (P=0.6) or after surgery (P=0.8). CONCLUSIONS: Although NCTs tend to have a lower final IOP compared with CTs, the latter are safe and effective and do not require surgical repositioning. Should a CT become occluded by the iris, an uncommon event in our study, it could be treated by laser iridotomy alone.

Glaucoma tube shunt implantation through the ciliary sulcus in pseudophakic eyes with high risk of corneal decompensation.

PURPOSE: To summarize our clinical experience with implanting Baerveldt glaucoma tube shunts through the ciliary sulcus in eyes with a posterior chamber intraocular lens and shallow anterior chambers, corneal transplants, guttata or edema. PATIENTS AND METHODS: A retrospective interventional nonrandomized noncomparative case series. Main outcome measure was postoperative corneal status. Secondary outcome measures included postoperative intraocular pressure (IOP), visual acuity and complications. RESULTS: Thirty-six eyes of 32 patients were identified through chart review. Follow-up period was 21.8+/-16.6 months (mean+/-standard deviation, range: 4.0 to 58.5 mo). At final visit, all 23 preoperative clear native corneas and 6 of 7 corneal transplants remained clear. Thus, of the 30 preoperative clear corneas, only 1 decompensated. Preoperative IOP was 27.9+/-11.8 mm Hg (range: 12 to 59 mm Hg), reduced postoperatively to 10.1+/-3.9 mm Hg (range: 2 to 21 mm Hg, P=0.0001), a reduction of 58.2%+/-19.3% (range: 5.0% to 95.4%). Final IOP was >or=5 and