Citations

Précis: When comparing patients on systemic immunosuppressive therapy to those without, there was no difference in intraocular pressure (IOP) early after SLT; however, at 1 year following SLT, IOP was higher in the immunosuppression group compared with controls. Purpose: To determine whether patients taking systemic immunosuppressive medications have a different IOP-lowering response to selective laser trabeculoplasty (SLT) compared with a control group of patients. Methods: All patients who underwent SLT at Mayo Clinic 2017–2021 were identified. Patients on systemic immunosuppressive medications at the time of SLT were compared with control patients not receiving systemic immunosuppressive medications. The primary endpoints of this study were the percentage IOP reduction at 1 to 2, 3 to 6, and 12 months. Additional analyses included the percentage of patients who did not require additional therapy at each time point. Results: There were 108 eyes of 72 patients that underwent SLT in the immunosuppressed group and 1997 eyes of 1417 patients in the control group. There was no significant difference in age-adjusted change in IOP between groups at the first postoperative visit 1 to 2 months following SLT (−18.8±20.7% vs. −16.0±16.5%, P=0.256) or 3–6 months following SLT (−15.2±21.6% vs. −18.3±23.2%, P=0.062). However, at 12 months following SLT, the IOP reduction in the immunosuppressive therapy group was significantly less compared with the control group (−15.1±21.2% vs. −20.3±22.9%, P=0.045). There was no difference between groups in the number of additional treatments during the study intervals. Conclusion: Patients in the systemic immunosuppressive therapy group showed equivalent early IOP-lowering after SLT compared with a control group, but the treatment response was diminished at 1 year. Further studies investigating IOP regulation after SLT in immunosuppressed patients are needed.

Glaucoma is the leading cause of irreversible blindness worldwide. Ocular biomechanical properties have been implicated in glaucoma pathogenesis, but existing commercial devices cannot determine changes in specific tissues. We recently performed a study to compare corneal wave speed (a measure of corneal elasticity) and ocular rigidity (a whole eye measurement of ocular biomechanics) between glaucomatous and normal eyes. Twenty glaucomatous eyes from 10 patients and 20 normal eyes from 13 controls, matched for age, intraocular pressure (IOP), and axial length were included. Ocular rigidity was calculated based on the difference in supine IOP by pneumatonometry with and without a 10-g weight. Corneal wave speed was determined by ultrasound surface wave elastography in which a small, 0.1 s harmonic vibration at 100 Hz was generated through the closed eyelids. Wave propagation was captured by an ultrasound transducer, and wave speed was determined from the phase change with distance. No significant differences in corneal wave speed between glaucomatous and normal eyes were detected (P = 0.17). However, ocular rigidity was significantly lower in glaucomatous eyes (0.0218 ± 0.0033 vs 0.0252 ± 0.0050 μl−1, P = 0.01). While lower ocular rigidity is consistent with altered biomechanics in glaucoma, the lack of a difference in corneal wave speed suggests that corneal tissue may not be significantly affected, and scleral changes likely play a more important role.

Papilledema is optic nerve swelling caused by increased intracranial hypertension, which has the potential to cause significant vision loss. Papilledema from idiopathic intracranial hypertension (IIH) is typically bilateral and symmetric, but can sometimes be asymmetric and even unilateral. The cause for this asymmetry is unknown. The purpose of this study was to develop ultrasound vibro-elastography (UVE) for assessing patients with papilledema to evaluate for biomechanical differences in these eyes. Nine patients with papilledema from IIH and 9 age-matched healthy control subjects were enrolled. A local harmonic vibration was used to generate wave propagation through the eyelid. Three excitation frequencies of 100, 150, and 200 Hz were used. A 6.4 MHz ultrasound probe was used to measure wave propagation in the eye structures. Wave speeds were measured in the posterior sclera of the maculae. The magnitudes of the wave speed of the IIH patients’ posterior sclera were significantly higher than those of healthy subjects. In patients with unilateral papilledema, the wave speed of the posterior sclera were higher in the eyes with papilledema than in the contralateral eyes without papilledema. UVE provides a noninvasive technique to measure the wave speed of posterior sclera, which is stiffer in eyes with papilledema.

ABSTRACT/SUMMARY Purpose Common LOXL1 protein-altering variants are significant genetic risk factors for exfoliation syndrome (XFS) and the related secondary glaucoma (XFG). A rare LOXL1 missense allele was associated with protective effects in a Japanese cohort, suggesting that other rare alleles may also exhibit protective effects. The goal of this study is to assess the contributions of rare LOXL1 variants to XFS/XFG risk in cases and controls from the United States (US). Methods LOXL1 rare variants (minor allele frequency (MAF) < 1%) were identified from Human exome BeadArray (Illumina) data for 1118 XFS/XFG cases and 3661 controls (Mass Eye and Ear (MEE) cohort) and from exome sequence data for 284 cases and 37,499 controls in All of Us (AoU) The distribution of rare variants, haplotypes, and diplotypes was examined using Fisher exact test. Results Four rare LOXL1 missense alleles, more common in controls, were identified in MEE, P= 7.6E-4), and 456 variants identified in AoU were found only in controls (P=0.045). The rare protective alleles were preferentially located (P= 5.8E-45) in a LOXL1 intrinsic disordered region (IDR) potentially involved in LOXL1 aggregation. Haplotypes that included the rare or minor variants were more common in controls compared to cases in both MEE (Odds Ratio (OR)= 0.21 (95% Confidence interval (CI): 0.19-0.24), P=1.7E-173) and AoU (OR=0.28 (95% CI: 0.23-0.34), P=4.4E-41), and heterozygous diplotypes were also significantly associated with reduced risk overall in both MEE (OR= 0.45 (95% CI: 0.52-0.39), P= 1.7E-89) and AoU (OR=0.26 (95% CI: 0.18-0.33, P=7.6E-28). Diplotypes comprised of only homozygous genotypes were associated with increased disease risk in both MEE and AoU (OR= 4.16 (95% CI: 3.60-4.76), P= 4.2E-89 and 5.26 (95% CI: 4.12-6.73), P=1.87E-42, respectively) and excess homozygosity and decreased heterozygosity was correlated with disease risk for common LOXL1 variants across multi-ethnic populations (P=1.0E-6). Conclusions Using exome array and exome sequence data from XFS/XFG cases and controls from the United States, we identified rare protective LOXL1 missense variants and show that the distribution of the corresponding haplotypes and diplotypes was associated with lower risk of XFS/XFG. Diplotype results also demonstrated that LOXL1 allelic heterozygosity was inversely associated, while homozygosity was associated with increased disease risk. These results suggest that LOXL1 MAF variation among populations, with corresponding variation in genotype heterozygosity and homozygosity, determines the XFS/XFG association.

Precis: Ocular biomechanics were compared between treated glaucoma patients and healthy subjects matched for age, intraocular pressure (IOP), and axial length. There was no difference in corneal wave propagation speed, but ocular rigidity was lower in glaucomatous eyes. Purpose: Ocular biomechanical properties are important in understanding glaucoma pathogenesis but the affected tissues are unclear. In this study, we compared corneal wave speed (a measure of corneal elasticity) and ocular rigidity coefficient between glaucomatous and normal eyes. Materials and Methods: Twenty glaucomatous eyes from 10 patients and 20 normal eyes from 13 controls, matched for age, IOP, and axial length were included. Ocular rigidity was calculated based on the difference in supine IOP by pneumatonometry with and without a 10-g weight. Corneal wave speed was determined by ultrasound surface wave elastography. A small, 0.1-second harmonic vibration at 100 Hz was generated through the closed eyelids. Wave propagation was captured by an ultrasound transducer, and wave speed was determined from the phase change with distance. Comparisons were performed using generalized estimating equation models. Results: There were no significant differences in corneal wave speed between glaucomatous and normal eyes (2.16±0.25 vs. 2.07±0.16 m/s, P=0.17). However, ocular rigidity was significantly lower in glaucomatous eyes (0.0218±0.0033 vs. 0.0252±0.0050/μL, P=0.01). Corneal wave speed was not correlated with age and IOP in either group (P≥0.23) but was correlated with ocular rigidity (R=0.48, P=0.02) and inversely correlated with axial length (R=−0.53, P=0.01) in glaucomatous eyes. Conclusion: Glaucomatous eyes tend to have lower ocular rigidity than healthy eyes with similar age, IOP, and axial length. However, the lack of a difference in corneal wave speed suggests that corneal tissue may not be significantly affected, and scleral changes likely play a more important role in glaucoma.

Precis: Diplopia was present in ~20% of patients with Ahmed FP7 (FP7) or Baerveldt 350 (B350), compared with 5% to 6% in those with Baerveldt 250 (B250) or controls, suggesting risk of diplopia should be included in preoperative counseling. Purpose: The purpose of this study was to examine the prevalence of diplopia and strabismus in patients with B250, B350, or FP7 glaucoma drainage devices (GDD). Materials and Methods: In this cohort study, glaucoma patients 18 years and above who had received, or would be receiving, a B250, B350, or FP7 GDD, and medically treated controls were consecutively enrolled from August 8, 2017, through July 31, 2019. The Diplopia Questionnaire was administered ≥30 days postoperatively, and upon enrollment to the controls. All diplopic patients underwent orthoptic measurements, which were reviewed by a strabismus specialist. Patients with GDDs in quadrants other than superotemporal, multiple GDDs, or scleral buckles were excluded. Bonferroni correction was applied for pairwise comparisons. Results: Diplopia was reported in 23/129 (17.8%) GDD patients and 5/99 (5.1%) control patients (P=0.003): 8/35 (22.9%) FP7, 2/32 (6.3%) B250, and 13/62 (21.0%) B350, with significant differences between FP7 versus controls (P=0.014) and B350 versus controls (P=0.011). Diplopia was attributable to GDD in 2 FP7 (5.9%, 95% confidence interval: 0.7-19.2), 0 B250, and 4 B350 (6.5%, 95% confidence interval: 1.7-15.2) patients, without significant differences between the GDDs. Conclusions: Patients with the larger (B350) or the higher profile plate (FP7) GDDs were more likely to experience diplopia than controls, and diplopia was attributable to the GDD in ~6% of patients with either a FP7 or a B350 GDD. Since diplopia can affect patients’ quality of life, preoperative counseling for GDD surgery, particularly B350 and FP7, should include a discussion of the risk of diplopia.

Abstract: The Rho kinase inhibitor netarsudil is a recently approved therapeutic option for the management of increased intraocular pressure in the United States. Although phase 3 clinical trials noted corneal changes related to the medication—namely, nonvisually-significant corneal verticillata—descriptions of a unique form of cystic epithelial edema began to surface as netarsudil (and its sister drug ripasudil, approved in Japan) gained widespread use. This series adds 3 new cases and reviews the current literature on this unique side effect.