The influence of etiology on surgical outcomes in neovascular glaucoma.

BACKGROUND: The authors sought to evaluate visual outcomes in patients with varying etiologies of neovascular glaucoma (NVG), who were treated with glaucoma drainage devices (GDD). METHODS: This was a retrospective case series of patients at a large academic teaching institution who had surgical intervention for neovascular glaucoma between September 2011 and May 2019. Eyes were included if there was documented neovascularization of the iris/angle with an intraocular pressure (IOP) > 21 mmHg at presentation. Eyes must also have been treated with surgical intervention that included a GDD. Primary outcome measure was visual acuity at the 1-year post-operative visit. Secondary outcome measure was qualified success after surgery defined by: pressure criteria (5 mmHg < IOP ≤ 21 mmHg), no re-operation for elevated IOP, and no loss of LP vision. RESULTS: One hundred twenty eyes met inclusion criteria. 61.7% had an etiology of proliferative diabetic retinopathy (PDR), 23.3% had retinal vein occlusions (RVO), and the remaining 15.0% suffered from other etiologies. Of patients treated with GDD, eyes with PDR had better vision compared to eyes with RVO at final evaluation (p = 0.041). There was a statistically significant difference (p = 0.027) in the mean number of glaucoma medications with Ahmed eyes (n = 70) requiring 1.9 medications and Baerveldt eyes (n = 46) requiring 1.3 medications at final evaluation. CONCLUSIONS: In our study, many patients with NVG achieved meaningful vision, as defined by World Health Organization (WHO) guidelines, and IOP control after GDD. Outcomes differed between patients with PDR and RVO in favor of the PDR group. Different GDD devices had similar performance profiles for VA and IOP outcomes. Direct prospective comparison of Baerveldt, Ahmed, and cyclophotocoagulation represents the next phase of discovery.

Risk Factors for Glaucoma Drainage Device Failure and Complication in the Pediatric Population.

PURPOSE: Report factors associated with failure and complication in a cohort of children who have undergone glaucoma drainage device (GDD) implantation. DESIGN: Retrospective case series. PARTICIPANTS: Consecutive pediatric GDD eyes that met criteria between May 1997 and July 2019. METHODS: Entries were included for analysis if age <18 years at the time of GDD implantation. Failure was defined as an intraocular pressure (IOP) greater than 21 mmHg or IOP reduction <20% or IOP <5 mmHg at 2 consecutive follow-up visits >3 months after implantation, reoperation for glaucoma, or loss of light perception vision. Complications were defined as postoperative events due to the GDD that required additional examination under anesthesia or additional surgery. MAIN OUTCOME MEASURES: Survival analyses of surgical failures and complications. RESULTS: Over a mean follow-up period of 5.4 years, 58 (38%) of 150 first-time GDD implants failed. Glaucoma associated with acquired conditions had decreased risk for failure when compared with glaucoma secondary to nonacquired systemic diseases (hazard ratio [HR], 12; P = 0.0063), nonacquired ocular anomalies (HR, 12; P = 0.0054), and primary congenital glaucoma (HR, 5.4; P = 0.041). There was an increased risk of failure for first-time tubes in younger patients with a 23% reduction of failure with each 3-year increase in age (HR, 0.77; P = 0.034). A total of 38 (25.3%) of the first-time GDD implantations had a complication. Higher preoperative IOP (5 mmHg increase; HR, 1.2; P = 0.038) and younger age (<3 years; HR, 2.1; P = 0.024; < 2 years, HR, 1.9; P = 0.046) increased the risk of complication. There were 22 second-time GDD implants in the study, of which 11 failed (50%), and increased risk for failure was associated with younger age at the time of implantation (<1 year; HR, 27; P = 0.0053) and concurrent glaucoma-related procedures with or without non-glaucoma anterior segment surgery at the time of implantation (HR, 13; P = 0.0085). CONCLUSIONS: Although GDD implantation in children is relatively safe and effective, these data should be interpreted in the context of children's relative longevity. These findings offer an outcome metric to which future novel glaucoma procedures in children can be compared.

Rates of RNFL Thinning in Patients with Suspected or Confirmed Glaucoma Receiving Unilateral Intravitreal Injections for Exudative AMD.

PURPOSE: This study evaluated whether the rate of retinal nerve fiber layer (RNFL) thinning is faster in eyes receiving intravitreal injections than in fellow uninjected eyes among patients suspected of having or confirmed to have glaucoma and exudative age-related macular degeneration (AMD). DESIGN: Retrospective comparative cohort study. METHODS: Patients with a diagnosis of unilateral exudative AMD and confirmed to have or suspected of having glaucoma in both eyes receiving unilateral intravitreal injections were identified. Those with ≥3 RNFL optical coherence tomography scans and ≥6 injections were included in the study. Rates of RNFL thinning in the injected eye versus the uninjected eye were estimated using linear mixed models. The main outcome measurement was the differences in rates of RNFL thinning in the injected versus the fellow uninjected eye. The effects of postinjection elevation of intraocular pressure (IOP), injection frequency, and number of injections were also evaluated. RESULTS: A total of 53 patients met the inclusion criteria, receiving 26.4 ± 15.9 intravitreal injections. The average rate of RNFL thinning in uninjected eyes was -0.620 µm/year (P = .029). Injected eyes had an additional incremental loss of -0.385 µm/year, but this value was not statistically significant (95% confidence interval [CI]: -1.147 to 0.379 µm/year; P = .324). Subgroup analysis with only glaucoma patients (n = 33) also demonstrated a nonsignificant effect of injections (-0.568 µm/year; 95% CI: -1.454 to 0.319 µm/year; P = .212). Postinjection IOP elevation, injection frequency, and total number of injections were not associated with faster RNFL loss. CONCLUSIONS: Among exudative AMD patients with glaucoma or suspected of having glaucoma, the rate of RNFL thinning in eyes receiving intravitreal injections did not significantly differ from that of fellow uninjected eyes.

Ocular trauma secondary to exercise resistance bands during the COVID-19 pandemic.

OBJECTIVE: To characterize injuries caused by exercise resistance bands. METHOD: Single-site retrospective case series of patients presenting to the Bascom Palmer Eye Institute emergency room with ocular injuries secondary to exercise resistance bands from March through September 2020. RESULTS: Eleven patients (9 males, 2 females, 14 eyes) were reviewed. Eight patients had a unilateral injury (3 right eyes, 5 left eyes) while 3 had bilateral injuries. Iritis was the most common presentation, seen in all 11 patients, followed by hyphema (9 patients, 82%), and vitreous hemorrhage (4 patients, 36%). Among affected eyes, the mean presenting visual acuity was approximately 20/100, improving to 20/40 on the last follow up (p = 0.06). However, 4 eyes (33%) had vision ≤20/60 at last follow up. CONCLUSIONS: Exercise resistance bands can cause a wide spectrum of ocular injuries, some leading to long-term vision loss. As such, we recommend that patients strongly consider using eye protection goggles or glasses while using resistance bands for exercise.

Idiopathic elevated episcleral venous pressure in a teenager.

PURPOSE: To report a case of unilateral idiopathic elevated episcleral venous pressure (IEEVP) in a 15-year-old patient. We reviewed and summarized published case reports of IEEVP to determine how to manage this challenging and rare condition. OBSERVATIONS: A 15-year-old Caucasian male presented with elevated intraocular pressures (IOP), blood in Schlemm canal in the left eye, and asymmetric cupping with corresponding glaucomatous findings on testing. We diagnosed the patient with IEEVP and describe successful surgical intervention with deep sclerectomy and viscocanalostomy. CONCLUSIONS AND IMPORTANCE: IEEVP is a diagnosis of exclusion and based on clinical findings of dilated episcleral veins, blood in Schlemm canal and glaucomatous changes. If glaucomatous progression occurs with medication, filtration surgery is usually required, and most patients have good results in the literature. Care should be taken to prevent post-operative hypotony and serous choroidal detachment.

Diagnostic Accuracy of Technology-based Eye Care Services: The Technology-based Eye Care Services Compare Trial Part I.

PURPOSE: Ophthalmologic telemedicine has the ability to provide eye care for patients remotely, and many countries have used screening tele-ophthalmology programs for several years. One such initiative at the Veterans Affairs (VA) Healthcare System is Technology-based Eye Care Services (TECS). The TECS services are located in primary care clinics and provide basic screening eye care, including vision, refraction, and retinal photography. Eye care providers ("readers") review the clinical data and recommend appropriate follow-up. One of the most common referrals from TECS has been for glaucoma, and this study was powered for glaucoma/glaucoma suspect detection. The current study was undertaken to identify aspects of the protocol that could be refined to enhance accuracy. DESIGN: Prospective comparison between the standard TECS protocol versus a face-to-face (FTF) examination on 256 patients, all of whom had no known history of significant ocular disease. PARTICIPANTS: Patients with no known ocular disease who were scheduled for an in-person eye appointment at the Atlanta VA. Patients underwent screening through the TECS protocol and received an FTF examination on the same day (gold standard). The TECS readers were masked to the results of the FTF examination. MAIN OUTCOME MEASURES: Percent agreement, kappa, sensitivity, and specificity were calculated for the TECS readers' interpretations versus the FTF examination. RESULTS: The TECS readers showed substantial agreement for cataract (κ ≥ 0.71) and diabetic retinopathy (κ ≥ 0.61) and moderate to substantial agreement for glaucoma/glaucoma suspect (κ ≥ 0.52) compared with an FTF examination. Age-related macular degeneration (AMD) showed moderate agreement (κ ≥ 0.34). Percent agreement with the TECS protocol was high (84.3%-98.4%) for each of the disease categories. Overall sensitivity and specificity were ≥75% and ≥55%, respectively, for any diagnosis resulting in referral. Inter-reader and intra-reader agreement was substantial for most diagnoses (κ > 0.61) with percent agreements ranging from 66% to 99%. CONCLUSIONS: Our results indicate that the standard TECS protocol is accurate when compared with an FTF examination for the detection of common eye diseases. The inclusion of additional testing such as OCT could further enhance diagnostic capability.

The Impact of OCT on Diagnostic Accuracy of the Technology-Based Eye Care Services Protocol: Part II of the Technology-Based Eye Care Services Compare Trial.

PURPOSE: Ophthalmologic telemedicine programs help to address the growing demand for eye care and lessen healthcare disparities for patients. One example is Technology-Based Eye Care Services (TECS), implemented in the Veteran Affairs Healthcare System in 2015. Accuracy and quality data for TECS both have been reported, and data suggest that although the TECS examination is comparable with an in-person examination, sensitivity for glaucoma and glaucoma suspect detection is less than that for other diseases, such as macular degeneration. Several articles suggest that OCT can improve disease detection for glaucoma. Therefore, this study was undertaken to test the impact of OCT on the accuracy of the TECS protocol. This article reports the data from part II of the TECS Compare trial; results from part I are discussed in a previous article. DESIGN: Prospective comparison between the TECS protocol with OCT versus a face-to-face (FTF) examination for 256 patients. PARTICIPANTS: An eligible patient was defined as a patient with no known ocular disease who desired a routine eye examination. METHODS: Patient underwent the TECS protocol workup and OCT nerve, OCT macula, and FTF examination on the same day. MAIN OUTCOME MEASURES: Percent agreement, κ values, sensitivity, and specificity were calculated for nonexpert readers after OCT interpretation of the TECS protocol using the FTF examination as the clinical gold standard. RESULTS: OCT did not improve the diagnostic accuracy of the TECS protocol when compared with an FTF examination. In most cases, OCT had no impact, and in the case of reader 2, OCT actually reduced the κ value from moderate agreement to agreement equal to chance while lowering the percent agreement by 10%. OCT also did not impact inter- or intrareader variability parameters. CONCLUSIONS: In this study, OCT did not seem to improve the accuracy of glaucoma or retinal disease detection when added to the standard TECS protocol. In one case, OCT worsened the agreement of the reader compared with the FTF. Further study is necessary to confirm these findings, and results may change if the readers are glaucoma or retina specialists instead of nonexpert OCT readers, comprehensive and anterior segment specialists.

Telocinobufagin, a Novel Cardiotonic Steroid, Promotes Renal Fibrosis via Na⁺/K⁺-ATPase Profibrotic Signaling Pathways.

Cardiotonic steroids (CTS) are Na⁺/K⁺-ATPase (NKA) ligands that are elevated in volume-expanded states and associated with cardiac and renal dysfunction in both clinical and experimental settings. We test the hypothesis that the CTS telocinobufagin (TCB) promotes renal dysfunction in a process involving signaling through the NKA α-1 in the following studies. First, we infuse TCB (4 weeks at 0.1 µg/g/day) or a vehicle into mice expressing wild-type (WT) NKA α-1, as well as mice with a genetic reduction (~40%) of NKA α-1 (NKA α-1+/-). Continuous TCB infusion results in increased proteinuria and cystatin C in WT mice which are significantly attenuated in NKA α-1+/- mice (all p < 0.05), despite similar increases in blood pressure. In a series of in vitro experiments, 24-h treatment of HK2 renal proximal tubular cells with TCB results in significant dose-dependent increases in both Collagens 1 and 3 mRNA (2-fold increases at 10 nM, 5-fold increases at 100 nM, p < 0.05). Similar effects are seen in primary human renal mesangial cells. TCB treatment (100 nM) of SYF fibroblasts reconstituted with cSrc results in a 1.5-fold increase in Collagens 1 and 3 mRNA (p < 0.05), as well as increases in both Transforming Growth factor beta (TGFb, 1.5 fold, p < 0.05) and Connective Tissue Growth Factor (CTGF, 2 fold, p < 0.05), while these effects are absent in SYF cells without Src kinase. In a patient study of subjects with chronic kidney disease, TCB is elevated compared to healthy volunteers. These studies suggest that the pro-fibrotic effects of TCB in the kidney are mediated though the NKA-Src kinase signaling pathway and may have relevance to volume-overloaded conditions, such as chronic kidney disease where TCB is elevated.

Early Experience with Technology-Based Eye Care Services (TECS): A Novel Ophthalmologic Telemedicine Initiative.

PURPOSE: The aging population is at risk of common eye diseases, and routine eye examinations are recommended to prevent visual impairment. Unfortunately, patients are less likely to seek care as they age, which may be the result of significant travel and time burdens associated with going to an eye clinic in person. A new method of eye-care delivery that mitigates distance barriers and improves access was developed to improve screening for potentially blinding conditions. We present the quality data from the early experience (first 13 months) of Technology-Based Eye Care Services (TECS), a novel ophthalmologic telemedicine program. DESIGN: With TECS, a trained ophthalmology technician is stationed in a primary care clinic away from the main hospital. The ophthalmology technician follows a detailed protocol that collects information about the patient's eyes. The information then is interpreted remotely. Patients with possible abnormal findings are scheduled for a face-to-face examination in the eye clinic. PARTICIPANTS: Any patient with no known ocular disease who desires a routine eye screening examination is eligible. METHODS: Technology-Based Eye Care Services was established in 5 primary care clinics in Georgia surrounding the Atlanta Veterans Affairs hospital. MAIN OUTCOME MEASURES: Four program operation metrics (patient satisfaction, eyeglass remakes, disease detection, and visit length) and 2 access-to-care metrics (appointment wait time and no-show rate) were tracked. RESULTS: Care was rendered to 2690 patients over the first 13 months of TECS. The program has been met with high patient satisfaction (4.95 of 5). Eyeglass remake rate was 0.59%. Abnormal findings were noted in 36.8% of patients and there was >90% agreement between the TECS reading and the face-to-face findings of the physician. TECS saved both patient (25% less) and physician time (50% less), and access to care substantially improved with 99% of patients seen within 14 days of contacting the eye clinic, with a TECS no-show rate of 5.2%. CONCLUSIONS: The early experience with TECS has been promising. Tele-ophthalmology has the potential to improve operational efficiency, reduce cost, and significantly improve access to care. Although further study is necessary, TECS shows potential to help prevent avoidable vision loss.

Elevated Plasma Marinobufagenin, An Endogenous Cardiotonic Steroid, Is Associated With Right Ventricular Dysfunction and Nitrative Stress in Heart Failure.

BACKGROUND: Plasma levels of cardiotonic steroids are elevated in volume-expanded states, such as chronic kidney disease, but the role of these natriuretic hormones in subjects with heart failure (HF) is unclear. We sought to determine the prognostic role of the cardiotonic steroids marinobufagenin (MBG) in HF, particularly in relation to long-term outcomes. METHODS AND RESULTS: We first measured plasma MBG levels and performed comprehensive clinical, laboratory, and echocardiographic assessment in 245 patients with HF. All-cause mortality, cardiac transplantation, and HF hospitalization were tracked for 5 years. In our study cohort, median (interquartile range) MBG was 583 (383-812) pM. Higher MBG was associated with higher myeloperoxidase (r=0.42, P<0.0001), B-type natriuretic peptide (r=0.25, P=0.001), and asymmetrical dimethylarginine (r=0.32, P<0.001). Elevated levels of MBG were associated with measures of worse right ventricular function (RV s', r=-0.39, P<0.0001) and predicted increased risk of adverse clinical outcomes (MBG≥574 pmol/L: hazard ratio 1.58 [1.10-2.31], P=0.014) even after adjustment for age, sex, diabetes mellitus, and ischemic pathogenesis. In mice, a left anterior descending coronary artery ligation model of HF lead to increases in MBG, whereas infusion of MBG into mice for 4 weeks lead to significant increases in myeloperoxidase, asymmetrical dimethylarginine, and cardiac fibrosis. CONCLUSIONS: In the setting of HF, elevated plasma levels of MBG are associated with right ventricular dysfunction and predict worse long-term clinical outcomes in multivariable models adjusting for established clinical and biochemical risk factors. Infusion of MBG seems to directly contribute to increased nitrative stress and cardiac fibrosis.

A polymorphic pseudoautosomal boundary in the Carica papaya sex chromosomes.

Sex chromosomes are defined by a non-recombining sex-determining region (SDR) flanked by one or two pseudoautosomal regions (PARs). The genetic composition and evolutionary dynamics of the PAR is also influenced by its linkage to the differentiated non-recombining SDR; however, understanding the effects of this linkage requires a precise definition of the PAR boundary. Here, we took a molecular population genetic approach to further refine the location of the PAR boundary of the evolutionary young sex chromosomes of the tropical plant, Carica papaya. We were able to map the position of the papaya PAR boundary A to a 100-kb region between two genetic loci approximately 2 Mb upstream of the previously genetically identified PAR boundary. Furthermore, this boundary is polymorphic within natural populations of papaya, with an approximately 100-130 kb expansion of the non-recombining SDR found in 16 % of individuals surveyed. The expansion of the PAR boundary in one Y haplotype includes at least one additional gene. Homologs of this gene are involved in male gametophyte and pollen development in other plant species.