Asher Weiner

Purpose. We describe a patient with normal tension glaucoma (NTG) of several years whose management was complicated by the presence of a giant internal carotid-ophthalmic artery aneurysm. Observations. A 72-year-old woman presented to our glaucoma clinic with accelerated deterioration of her vision in her left eye (OS) over a 1-month period. Her ophthalmic history was most notable for bilateral NTG diagnosed 3 years prior which had been treated with several laser trabeculoplasty OS and topical bimatoprost 0.01% eye drops in both eyes (OU). Upon evaluation, her visual acuity OS had worsened, and visual field (VF) testing showed extensive progressive losses temporally and pericentrally OS over a year with stable IOP measurements and no neurological complaints. Given her atypical NTG progression, she was referred for an urgent neurological evaluation which revealed an unruptured giant left internal carotid-ophthalmic aneurysm. Following the successful treatment of the aneurysm with platinum coils, she continued to demonstrate additional bilateral ophthalmic changes including further progression of VF loss and RNFL thinning on follow-up. Conclusion and Importance. Overall, this report describes a unique complication in the management of a patient with chronic bilateral NTG in the form of a giant internal carotid-ophthalmic aneurysm. Moreover, it highlights the need for clinicians to maintain a degree of suspicion for compressive lesions of the optic nerve when presented with atypical progression of VFs and/or visual acuity loss in glaucomatous patients.

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.

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.

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.

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. (C) 2018 ASCRS and ESCRS

Purpose: To create a highly balanced comparison of ab interno trabeculectomy (Trabectome, AIT) and trabecular bypass stenting (iStent, TBS).Setting: Eye and Ear Institute, Pittsburgh, Ross Eye Institute, Buffalo, and Glaucoma Associates of Texas, Dallas, USA.Design: Retrospective Exact Matching analysis.Methods: AIT and TBS patients were included from three large glaucoma practices. The primary outcome measure was the unmedicated IOP ≤ 21 mmHg at 2-year follow-up visit. A secondary measure was unmedicated IOP reduction ≥ 20% at 2 years. Patients were matched by baseline IOP, the number of glaucoma medications and glaucoma type using Exact Matching and by age using Nearest Neighbor matching. Patients without a close match were excluded. All surgeries were combined with phacoemulsification. Results: 154 AIT and 110 TBS eyes were analyzed. 48 AIT patients were exactly matched to 48 TBS patients. Both groups had a baseline IOP of 15.3±3.1 mmHg. At 24 months, the mean IOP was 13.9±3.3 for AIT versus 16.8±2.8 mmHg for TBS (p=0.04), while the number of medications was 0.7±1.0 for AIT versus 1.7±1.2 for TBS (p=0.04). The proportion of subjects achieving IOP ≤ 21 mmHg without medications at 24 months was 53% in AIT versus 16.6% in TBS (P < 0.05). At 24-month follow up 17.6% of patients in AIT had ≥ 20% IOP reduction without medication versus no patient in TBS. Conclusions: An Exact Matching comparison of AIT and TBS demonstrated greater IOP reduction with fewer medications in AIT.

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.