Haptic curing with endolaser after lens tilt in the Yamane technique.

Purpose: To describe a case of intraocular lens (IOL) tilt following transscleral IOL fixation with the Yamane technique and subsequent correction of tilt using 810-nm endoscopic diode laser. Observations: Our patient required lens exchange and secondary IOL implantation due to a dislocated 1-piece IOL in the bag causing iris chafe. After routine IOL fixation with the Yamane technique and a Zeiss CT Lucia 602 lens, the IOL tilted significantly in the immediate postoperative period. The lens tilt was subsequently corrected in the operating room using endolaser to melt and reshape (cure) the optic-haptic junction. Conclusions: IOL tilt is a known complication associated with the Yamane technique, which has seen increasing reports with the Zeiss CT Lucia 602 lens. Using endolaser to reconfigure the tilted optic into the desired orientation is a more novel procedure that can correct the lens tilt without the need for IOL exchange.

Migraine is a risk factor for pseudophakic positive dysphotopsia following monofocal lens implantation.

OBJECTIVE: To identify neuroadaptation-related risk factors for persistent positive dysphotopsia (>6 months) following monofocal lens implantation. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients of an academic institution and a private practice in Saint Louis, Missouri. Inclusion criteria were adults with cataract extraction between January 2010 and April 2021 with monofocal intraocular lens implantation. Exclusion criteria included dementia, <20/40 acuity, visual pathway damage, visual field loss, and significant pathology causing photopsia. METHODS: Participants were surveyed via telephone. RESULTS: There were 385 participants (385 eyes), of whom 66 had persistent dysphotopsia (58 positive), 298 had none, and 21 had nonpersistent dysphotopsia. Among the 58 who had positive persistent dysphotopsia, mean Pseudophakic Dysphotopsia Questionnaire 6 (PDQ-6) score was 14.11 (SD, 8.46). There were no significant differences in sex or race. Migraine prevalence was greater among those with dysphotopsia (21.2%) than among those without (11.4%; p = 0.054). History of migraine was associated with an increase in PDQ-6 score of 2.76 points (p = 0.006). Six people in each group had Visual Aura Rating Scale (VARS) scores greater than zero. Mean VARS score was 0.48 for those with dysphotopsia and 0.14 for those without (p = 0.03). History of migraine or increased VARS score, younger age, and female sex were associated with lower satisfaction. CONCLUSION: History of migraine was associated with increased dysphotopsia severity and decreased patient satisfaction. Although further study with a larger sample size is warranted, these preliminary results highlight the potential of simple questions to individualize lens choice, reduce the risk of dysphotopsia, and improve patient satisfaction.

Severe Spontaneous Tilt of Scleral-Fixated Intraocular Lenses.

PURPOSE: To report and evaluate a multicenter series of 18 cases of severe, spontaneous IOL tilt involving the flanged intrascleral haptic fixation technique (FISHF). DESIGN: Clinical study with historical controls. METHODS: We report a cross-sectional study of 46 FISHF cases using the CT Lucia 602 IOL at a single academic center over a period of 24 weeks to determine the incidence of severe rotisserie-style rotational tilt. These rates were then compared with the same time-frame the prior year to help determine if this is a new phenomenon. Additional cases of severe tilt were solicited from another 4 academic centers. RESULTS: Among 46 FISHF cases at a single center, 5 developed severe tilt. No clear pattern in surgical technique, ocular history, or ocular anatomy was evident in these cases compared with controls, although the involved IOLs clustered within a narrow diopter range, indicative of a batch effect. In the same 24-week interval the year before, 33 FISHF cases were performed, none of which exhibited severe rotational tilt. In our multicenter dataset, 18 cases of tilt were identified. Surgeons included fellow and early-career physicians as well as surgeons with multiple years of experience with the Yamane technique. A variety of surgical approaches for FISHF were represented. In at least 8 of the cases, haptic rotation and/or dehiscence at the optic-haptic junction were documented. CONCLUSIONS: The identification of haptic rotation and dehiscence intraoperatively in several cases may reflect a new stability issue involving the optic-haptic junction.

Corneal endothelial safety profile in minimally invasive glaucoma surgery.

PURPOSE: To compare 5-year corneal endothelial safety of 3 minimally invasive glaucoma surgery (MIGS) devices (iStent inject , Hydrus Microstent, CyPass Micro-Stent). SETTING: U.S. multicenter trials. DESIGN: Post hoc 5-year analysis from prospective randomized single-masked pivotal trials. METHODS: Mild to moderate open-angle glaucoma subjects received a MIGS implant with phacoemulsification (implant + phaco) or phaco alone (control). In addition, 5-year end points comparing the implant and control groups included proportion of eyes with significant endothelial cell loss (ECL) (>30% or ≥30% vs baseline) and mean endothelial cell density (ECD). RESULTS: Comparable proportions of eyes in the iStent inject + phaco and control groups had significant 60-month ECL (9.4% vs 6.3%, respectively, diff: 3.2%, 95% CI, -5.0% to 11.3%, P = .77). Hydrus (20.8% vs 10.6%, diff: 10.2%, 95% CI, 3.2% to 17.2%, P = .01) and CyPass (27.2% vs 10.0%, diff: 17.2%, 95% CI, 5.6% to 28.7%, P = .02) had more eyes with ECL vs controls (iStent inject 1.49X, Hydrus 1.96X, CyPass 2.72X vs controls). Mean ECD over 60 months for iStent inject was indistinguishable vs control, whereas greater ECL was observed primarily 3 months postoperative (Hydrus) or accelerated after 2 years (CyPass). No iStent inject or Hydrus subjects developed persistent corneal edema, whereas 7 CyPass-implanted eyes developed ECL-related complications. CONCLUSIONS: Through 5 years postoperative, there were no differences in proportion of eyes with significant ECL or mean ECD between the iStent inject and control groups. There was greater 5-year ECL and lower ECD in the Hydrus and CyPass groups vs controls. The Hydrus ECL rate mirrored control after 3 months; the CyPass ECL rate accelerated vs control.

Glaucoma surgical procedures under development.

PURPOSE OF REVIEW: Rapid innovation in glaucoma surgery is expanding surgical options in the angle, subconjunctival space, and supraciliary space. RECENT FINDINGS: Advancements in glaucoma surgery make it possible for surgeons to provide treatments with less risk. In particular, new devices and lasers are available for minimally invasive glaucoma surgeries. There are also new implants and techniques for bleb-forming glaucoma surgery. SUMMARY: As glaucoma surgeons have access to an increasing number of procedures, devices, and treatments, it is important for evidence to drive decision-making.

Alternatives to Topical Glaucoma Medication for Glaucoma Management.

Topical glaucoma medications have favorable safety and efficacy, but their use is limited by factors such as side effects, nonadherence, costs, ocular surface disease, intraocular pressure fluctuations, diminished quality of life, and the inherent difficulty of penetrating the corneal surface. Although traditionally these limitations have been accepted as an inevitable part of glaucoma treatment, a rapidly-evolving arena of minimally invasive surgical and laser interventions has initiated the beginnings of a reevaluation of the glaucoma treatment paradigm. This reevaluation encompasses an overall shift away from the reactive, topical-medication-first default and a shift toward earlier intervention with laser or surgical therapies such as selective laser trabeculoplasty, sustained-release drug delivery, and micro-invasive glaucoma surgery. Aside from favorable safety, these interventions may have clinically important attributes such as consistent IOP control, cost-effectiveness, independence from patient adherence, prevention of disease progression, and improved quality of life.

New Devices in Glaucoma.

Glaucoma remains a leading cause of blindness globally. Minimally invasive treatment techniques are rapidly expanding the availability of therapeutic options for glaucoma. These include devices aimed at enhancing outflow through the subconjunctival space, Schlemm's canal, and suprachoroidal space, sustained-release drug delivery devices, and extraocular devices aiming to reduce glaucomatous progression through other novel means. In this review, we provide an overview of several novel devices either newly available or in development for the medical and surgical management of glaucoma. Further studies are required to determine the long-term efficacy of these devices and how they will integrate into the current landscape of glaucoma management.

Long-Term Endothelial Safety Profile With iStent Inject in Patients With Open-Angle Glaucoma.

PURPOSE: To report 5-year postoperative safety data of iStent inject, including overall stability, endothelial cell density (ECD), and endothelial cell loss (ECL) in patients with mild-to-moderate primary open-angle glaucoma (POAG). DESIGN: 5-year follow-up safety study of the prospective, randomized, single-masked, concurrently controlled, multicenter iStent inject pivotal trial. METHODS: In this 5-year follow-up safety study of the 2-year iStent inject pivotal randomized controlled trial, patients receiving iStent inject placement and phacoemulsification or phacoemulsification alone were studied for the incidence of clinically relevant complications associated with iStent inject placement and stability. Corneal endothelial endpoints were mean change in ECD from screening and proportion of patients with >30% ECL from screening, from analysis of central specular endothelial images by a central image analysis reading center at several time points through 60 months postoperatively. RESULTS: Of the 505 original randomized patients, 227 elected to participate (iStent inject and phacoemulsification group, n = 178; phacoemulsification-alone control group, n = 49). No specific device-related adverse events or complications were reported through month 60. No significant differences were observed in mean ECD, mean percentage change in ECD, or proportion of eyes with >30% ECL between the iStent inject and control groups at any time point; mean percentage decrease in ECD at 60 months was 14.3% ± 13.4% in the iStent inject group and 14.8% ± 10.3% in the control group (P = .8112). The annualized rate of ECD change from 3 to 60 months was neither clinically nor statistically significant between groups. CONCLUSIONS: Implantation of iStent inject during phacoemulsification in patients with mild-to-moderate POAG did not produce any device-related complications or ECD safety concerns compared to phacoemulsification alone through 60 months.

Gel Stent Versus Trabeculectomy: The Randomized, Multicenter, Gold-Standard Pathway Study (GPS) of Effectiveness and Safety at 12 Months.

PURPOSE: To compare effectiveness and safety of the gel stent to trabeculectomy in open-angle glaucoma (OAG). DESIGN: Prospective, randomized, multicenter, noninferiority study. METHODS: Patients with OAG and intraocular pressure (IOP) 15 to 44 mm Hg on topical IOP-lowering medication were randomized 2:1 to gel stent implantation or trabeculectomy. Primary end point (surgical success): percentage of patients at month 12 achieving ≥20% IOP reduction from baseline without medication increase, clinical hypotony, vision loss to counting fingers, or secondary surgical intervention (SSI) in a noninferiority test with 24% margins. Secondary end points (month 12) included mean IOP and medication count, postoperative intervention rate, visual recovery, and patient-reported outcomes (PROs). Safety end points included adverse events (AEs). RESULTS: At month 12, the gel stent was statistically noninferior to trabeculectomy (between-treatment difference [Δ], -6.1%; 95% CI, -22.9%, 10.8%); 62.1% and 68.2% achieved the primary end point, respectively (P=.487); mean IOP and medication count reductions from baseline were significant (P<.001); and the IOP change-related Δ (2.8 mm Hg) favored trabeculectomy (P=.024). The gel stent resulted in fewer eyes requiring in-office postoperative interventions (P=.024 after excluding laser suture lysis), faster visual recovery (P≤.048), and greater 6-month improvements in visual function problems (ie, PROs; P≤.022). The most common AEs were reduced visual acuity at any time (gel stent, 38.9%; trabeculectomy, 54.5%) and hypotony (IOP <6 mm Hg at any time) (gel stent, 23.2%; trabeculectomy, 50.0%). CONCLUSIONS: At month 12, the gel stent was statistically noninferior to trabeculectomy, per the percentage of patients achieving ≥20% IOP reduction from baseline without medication increase, clinical hypotony, vision loss to counting fingers, or SSI. Trabeculectomy achieved a statistically lower mean IOP, numerically lower failure rate, and numerically lower need for supplemental medications. The gel stent resulted in fewer postoperative interventions, better visual recovery, and fewer AEs.

Intraocular Pressure and Medication Changes Associated with Xen Gel Stent: A Systematic Review of the Literature.

The Xen gel stent (Allergan Inc, an AbbVie company; Dublin, Ireland) was conceived as an option for patients requiring modest IOP reduction but for whom trabeculectomy was not yet indicated. As with any glaucoma surgery, establishing criteria for patient selection and identifying factors that contribute to a high likelihood of success are important. To help guide clinical decision-making, a systematic review of published studies on the gel stent was performed, with the goal of understanding postoperative outcomes based on clinical and patient factors. Results were organized around a series of pertinent clinical questions based on scenarios encountered in clinical practice. Criteria for including studies were intentionally broad, with the objective of simulating the diverse population of glaucoma patients encountered in real-world practice. Outcomes for IOP and medication reduction postoperatively were assessed in various analyses, including in eyes with various glaucoma types and severity; in eyes naïve to surgery as well as those with a history of prior incisional glaucoma surgery; and when surgery was performed as a standalone procedure or at the time of cataract surgery. The results of each of the various analyses were consistent in demonstrating that successful gel stent surgery achieved a postoperative IOP of approximately 14.0 mm Hg and reduction to fewer than 1 glaucoma medication. Additional data are shown on outcomes by method of implant (ab interno vs ab externo); intraoperative use of antifibrotics; and rates of needling in published studies.

Extreme intraocular pressure and steroid-dependent iritis.

A 50-year-old ophthalmic technician was referred by her retina specialist for urgent consultation due to markedly elevated intraocular pressure (IOP) unresponsive to medical therapy. Her history included chronic polyarticular juvenile rheumatoid arthritis and chronic uveitis requiring ongoing topical steroid therapy. She had a sub-Tenon injection of Kenalog (triamcinolone) 18 months prior to referral. Chronic topical anti-inflammatory therapy included nepafenac (Ilevro) and prednisolone acetate 2 times a day. Attempts to discontinue topical steroid resulted in worsening inflammation. The patient was referred when the IOP measured 44 mm Hg in the left eye despite aggressive medical therapy, including acetazolamide. The IOP improved slightly when loteprednol was substituted for prednisolone acetate. Current medications in the left eye include brimonidine 3 times a day, loteprednol 2 times a day, nepafenac 2 times a day, and fixed combination latanoprost + netarsudil at bedtime. Her only medication in the right eye was travoprost. She is intolerant to dorzolamide. She was also taking acetazolamide 500 mg 2 times a day. She was not taking any anticoagulants. Past surgical history included cataract surgery in each eye. She has not had laser trabeculoplasty in either eye. Examination revealed uncorrected visual acuity of J1+ in the right eye (near) and 20/30 in the left eye (mini-monovision). There was no afferent pupillary defect. There was mild band keratopathy in each eye while the central cornea was clear in both eyes without keratic precipitates. Here angles were open to gonioscopy without peripheral anterior synechia. There was mild to moderate flare in each eye with trace cells. The IOP was 17 mm Hg in the right eye and 31 mm Hg in the left. Central corneal thickness measured 560 µm and 559 µm in the right and left eye respectively. There was a well-positioned intraocular lens within each capsule with a patent posterior capsulotomy. There was mild vitreous syneresis but no vitreous cell. The cup to disc ratio was 0.5 in each eye with a symmetrical neural rim. The retina was flat without macular edema. Visual field was normal in both eyes (Figures 1 and 2). Optical coherence tomography of retinal nerve fiber layer (RNFL) is shown in Figure 3 and retinal ganglion cell layer is shown in Supplemental Figure 1 (http://links.lww.com/JRS/A756).JOURNAL/jcrs/04.03/02158034-202301000-00020/figure1/v/2022-12-26T045736Z/r/image-tiffJOURNAL/jcrs/04.03/02158034-202301000-00020/figure2/v/2022-12-26T045736Z/r/image-tiffJOURNAL/jcrs/04.03/02158034-202301000-00020/figure3/v/2022-12-26T045736Z/r/image-tiff Please comment on your management of this patient's left eye.

Single Administration of Intracameral Bimatoprost Implant 10 µg in Patients with Open-Angle Glaucoma or Ocular Hypertension.

INTRODUCTION: This study evaluated the intraocular pressure (IOP)-lowering efficacy and safety of a single intracameral administration of bimatoprost implant 10 µg in adults with open-angle glaucoma or ocular hypertension. METHODS: Two identically designed, randomized, 20-month, parallel-group, phase 3 clinical trials (one study eye/patient) compared three administrations of 10- or 15-µg bimatoprost implant (day 1, weeks 16 and 32) with twice-daily topical timolol maleate 0.5%. An open-label, 24-month, phase 1/2 clinical trial compared one or two implants administered in the study eye with once-daily topical bimatoprost 0.03% in the fellow eye. Separate analyses of the pooled phase 3 and phase 1/2 study datasets evaluated outcomes in the 10-µg bimatoprost implant and comparator treatment arms after a single implant administration, up to the time of implant re-administration or rescue with IOP-lowering medication. RESULTS: In the phase 3 studies, 10-µg bimatoprost implant single administration demonstrated IOP reductions (hour 0) of 4.9-7.0 mmHg through week 15 from a mean (standard deviation, SD) baseline IOP of 24.5 (2.6) mmHg (n = 374); IOP in the topical timolol BID group was reduced by 6.0-6.3 mmHg from a mean (SD) baseline IOP of 24.5 (2.6) mmHg (n = 373). In the phase 1/2 study (n = 21), median time to use of additional IOP-lowering treatment (Kaplan-Meier analysis) was 273 days (approximately 9 months), and 5 of 21 enrolled patients (23.8%) required no additional IOP-lowering treatment up to 24 months after single administration. In each study, after a single implant administration there were no reports of corneal edema, corneal endothelial cell loss, or corneal touch, and no patients had 20% or greater loss in corneal endothelial cell density. CONCLUSIONS: Bimatoprost implant single administration lowers IOP and has a favorable safety profile. Additional studies are needed to further evaluate the duration of effect and factors predicting long-term IOP lowering after a single implant administration. TRIAL REGISTRATION NUMBERS: ClinicalTrials.gov NCT02247804, NCT02250651, and NCT01157364.

An Alternate Technique for Goniotomy: Description of Procedure and Preliminary Results.

Purpose: Multiple glaucoma treatment modalities seek to lower IOP by bypassing or removing a portion of the juxtacanalicular trabecular meshwork. These procedures often require expensive implants or specialized surgical instruments. The authors developed a technique for ab interno goniectomy utilizing a standard disposable 25-gauge hypodermic needle. The surgical procedure-termed bent ab interno needle goniectomy (BANG)-and preliminary results are presented here. Methods: A retrospective chart review was performed for all patients who underwent goniotomy using a modified hypodermic needle by one of the three authors between July 2017 and June 2018. The mean and standard deviation pre- and postoperative IOP and the number of glaucoma medications were calculated. The student paired t-test was used to compare pre- and postoperative data. A P-value of < 0.05 was considered statistically significant. Results: At postoperative month six, the mean IOP was 13.3 ± 2.5 mmHg (P = 3.6 × 10 - 7 ) on 0.5 ± 0.8 topical glaucoma medications (P = 0.01). A ≥ 20% reduction in IOP was achieved in 73% of patients. Seventy-three percent of patients required ≥ 1 fewer medication, while 73% of patients required no medications for IOP control. Forty-one percent of those treated achieved IOP ≤ 12 mmHg. Conclusion: The BANG procedure is a low-cost MIGS technique available to surgeons around the world with preliminary outcomes similar to more expensive alternatives.

Compatibility and durability of the gel stent material.

INTRODUCTION: The XEN Gel Stent (AbbVie Pharmaceuticals) is a device made from Gelatin; a well-known material in the medical field that is firm enough to hold its shape and soft enough to conform to tissues and reduce the risk of erosion. The Gel Stent creates a permanent outflow connection between the anterior chamber and subconjunctival space. AREAS COVERED: Validation testing done on the Gel Stent to evaluate biocompatibility and durability of the material as well as real-world experience are included and discussed in this paper. EXPERT OPINION: Correlating the results of the preclinical testing, study outcomes available in the published literature, and the surgeons' experiences, the device and materials have shown to have an acceptable biocompatibility and durability profile, with a stable, nondegradable, and permanent implant.

Reoperation Rates and Disease Costs for Primary Open-Angle Glaucoma Patients in the United States Treated with Incisional Glaucoma Surgery.

PURPOSE: To evaluate the claims-based 5-year economic and reintervention burden for patients with primary open-angle glaucoma (POAG) after incisional glaucoma surgery in the United States. DESIGN: Retrospective Medicare claims analysis. PARTICIPANTS: One thousand nine hundred forty-five Medicare fee-for-service patients with POAG treated with trabeculectomy, tube shunt, or EX-PRESS shunt procedures from 2010 through 2011. METHODS: Patients with POAG treated with incisional glaucoma surgery (trabeculectomy, tube shunt, or EX-PRESS shunt) from 2010 through 2011 were identified in the Medicare 5% Standard Analytical Files. Ten years of claims data for each patient (2005-2016) were evaluated for prior incisional surgeries and downstream procedures in the treated eye within 5 years of index. Patients' characteristics, downstream procedures, and POAG-related costs were evaluated. Proportions of patients with downstream procedures in the index eye indicating failure of the index surgery, glaucoma reoperations, nonfailure complications, interventions, or cataract surgery were assessed over 5 years of follow-up. MAIN OUTCOME MEASURES: Cumulative rates of index surgery failure and glaucoma reoperations over 5 years after incisional glaucoma surgery. RESULTS: Of 1945 patients, 223 underwent EX-PRESS shunt, 551 underwent tube shunt, and 1171 underwent trabeculectomy at index. Rates of failure, glaucoma reoperations, or nonfailure complications rose over 5 years after index for all patient subgroups. At 1 year, 15.1% of EX-PRESS shunt patients, 11.6% of tube shunt patients, and 8.8% of trabeculectomy patients had experienced failure based on postindex procedures. By 5 years follow-up, these rates were 31.5% of EX-PRESS shunt patients, 27.1% of tube shunt patients, and 23.5% of trabeculectomy patients. Five-year rates of glaucoma reoperations were 18.3%, 14.0%, and 15.1%, respectively. Among tube shunt and trabeculectomy patients with prior incisional surgery, the 5-year failure rates were 32.5% and 32.6%, and reoperations rates were 12.0% and 26.1%, respectively. CONCLUSIONS: More than one-fourth of patients with POAG treated with incisional surgery underwent additional procedures to address index surgery failure within 5 years. Of these, more than half underwent additional incisional glaucoma surgery. These outcomes from clinical practice settings demonstrate that patients with POAG who require incisional surgery continue to need additional safe and effective surgical treatment options to manage their glaucoma.

Compositional Analysis of Extracellular Aggregates in the Eyes of Patients With Exfoliation Syndrome and Exfoliation Glaucoma.

Purpose: Exfoliation syndrome (XFS) is a condition characterized by the production of insoluble fibrillar aggregates (exfoliation material; XFM) in the eye and elsewhere. Many patients with XFS progress to exfoliation glaucoma (XFG), a significant cause of global blindness. We used quantitative mass spectrometry to analyze the composition of XFM in lens capsule specimens and in aqueous humor (AH) samples from patients with XFS, patients with XFG and unaffected individuals. Methods: Pieces of lens capsule and samples of AH were obtained with consent from patients undergoing cataract surgery. Tryptic digests of capsule or AH were analyzed by high-performance liquid chromatography-mass spectrometry and relative differences between samples were quantified using the tandem mass tag technique. The distribution of XFM on the capsular surface was visualized by SEM and super-resolution light microscopy. Results: A small set of proteins was consistently upregulated in capsule samples from patients with XFS and patients with XFG, including microfibril components fibrillin-1, latent transforming growth factor-ß-binding protein-2 and latent transforming growth factor-ß-binding protein-3. Lysyl oxidase-like 1, a cross-linking enzyme associated with XFS in genetic studies, was an abundant XFM constituent. Ligands of the transforming growth factor-ß superfamily were prominent, including LEFTY2, a protein best known for its role in establishing the embryonic body axis. Elevated levels of LEFTY2 were also detected in AH from patients with XFG, a finding confirmed subsequently by ELISA. Conclusions: This analysis verified the presence of suspected XFM proteins and identified novel components. Quantitative comparisons between patient samples revealed a consistent XFM proteome characterized by strong expression of fibrillin-1, lysyl oxidase-like-1, and LEFTY2. Elevated levels of LEFTY2 in the AH of patients with XFG may serve as a biomarker for the disease.

Longitudinal Growth Differentiation Factor 15 (GDF15) and Long-term Intraocular Pressure Fluctuation in Glaucoma: A Pilot Study.

PURPOSE: Growth Differentiation Factor 15 (GDF15) was previously identified as a molecular marker of retinal ganglion cell stress in rodent models of glaucoma and was elevated in the aqueous humor (AH) of patients with primary open-angle glaucoma as a possible risk factor for glaucoma progression. The purpose of this study was to determine whether changes in the AH GDF15 levels were associated with intraocular pressure (IOP) changes in eyes undergoing glaucoma surgery. METHODS: Here, we performed a prospective, longitudinal pilot study in nine patients to determine whether changes in AH GDF15 levels from surgery to post-surgery follow-up were associated with IOP fluctuation. An initial AH sample was taken from the peripheral corneal paracentesis during planned glaucoma surgery, and a second sample was taken during an outpatient follow-up visit, approximately six months later. RESULTS: There was a statistically significant correlation between GDF15 fold change and IOP standard deviation (r = 0.87, P = 0.003), IOP range (r = 0.87, P = 0.003), and maximum IOP (r = 0.86, P = 0.003). There was no correlation between the GDF15 fold change and baseline IOP (r = 0.50, P = 0.17), final IOP (r = 0.038, P = 0.92), or mean IOP (r = 0.40, P = 0.28). CONCLUSION: Our findings in this pilot study suggest that longitudinal changes in AH GDF15 may be associated with IOP fluctuation during the postoperative period. Further studies are necessary to corroborate these findings in a larger patient population and to explore the possibility that AH GDF15 may be used not only to improve treatment algorithms but also as a surrogate endpoint in clinical trials.

Increased Aqueous Humor GDF15 Is Associated with Worse Visual Field Loss in Pseudoexfoliative Glaucoma Patients.

Purpose: To determine whether increased growth differentiation factor 15 (GDF15) in aqueous humor (AH) is associated with worse visual field loss in patients with pseudoexfoliative glaucoma (PXG). Methods: We recruited 12 patients (6 males, 6 females) with primary open-angle glaucoma (POAG) or PXG who were scheduled to undergo glaucoma surgery. AH was obtained from the initial peripheral paracentesis for the planned glaucoma surgery, and GDF15 levels were quantified with enzyme-linked immunosorbent assay by an investigator masked to clinical information. Humphrey visual field testing was performed as a part of routine care; results were obtained by reviewing the medical record. Results: AH GDF15 was detectable in patients with POAG and PXG. Increased AH GDF15 was significantly associated with worse mean deviation in patients with POAG (r = -0.94; 95% confidence interval [CI], -0.99 to -0.33; P = 0.02) and PXG (r = -0.92; 95% CI, -0.99 to -0.41; P = 0.01). Conclusions: AH GDF15 is detectable in patients with PXG and POAG. Elevated AH GDF15 is strongly associated with worse mean deviation in both subgroups. These findings suggest that GDF15 may be a molecular marker of glaucoma severity that is generalizable to multiple types of glaucoma regardless of the underlying etiology. Translational Relevance: This study provides proof of concept that GDF15, a molecular marker of retinal ganglion stress that was initially identified in rodent models, may have clinical utility as a measure of glaucoma severity not only in POAG but also in PXG.

Comparative Outcomes of the Molteno3 and Baerveldt Glaucoma Implants.

PURPOSE: To compare outcomes between 2 nonvalved glaucoma drainage devices (GDDs) used to treat refractory glaucoma or in patients with neovascular/uveitic glaucoma likely to be poorly responsive to less aggressive therapies. DESIGN: Retrospective, nonrandomized, multicenter comparative study. PARTICIPANTS: A total of 117 eyes from 117 patients. METHODS: Retrospective chart review of patients who underwent implantation of the Baerveldt (BGI) (Abbott Medical Optics, Abbott Park, IL) or the Molteno3 glaucoma implant (MGI) (Molteno Ophthalmic Limited, Dunedin, New Zealand). Noninferiority of the MGI versus the BGI was tested with Cox and mixed-effects regression models. Interventions in each group were analyzed with chi-square tests. MAIN OUTCOME MEASURES: The primary outcome was time until device failure, defined as intraocular pressure (IOP) >21 mmHg or a reduction <20%, hypotony, reoperation for glaucoma, or loss of light perception. Secondary outcomes were intraoperative time, postoperative IOP, number of IOP-lowering medications, and visual acuity (VA). RESULTS: The MGI could not be deemed noninferior to the BGI with regard to time until device failure (hazard ratio [HR], 0.83; confidence interval [CI], 0.41-1.65). The MGI was noninferior to the BGI when comparing postoperative IOP, a difference of -0.40 mmHg (95% CI, -1.74-0.93). The MGI needed 2% fewer medications (ratio of 0.98, 95% CI, 0.79-1.22), but noninferiority could not be claimed. With regard to VA, the MGI's mean was 0.10 logarithm of the minimum angle of resolution (logMAR) higher (95% CI, -0.01-0.21), but noninferiority testing was again inconclusive. Intraoperative time for the MGI was 15.7 minutes shorter versus the 350 mm2 plate size BGI (P < 0.001) and 4.3 minutes shorter versus the 250 mm2 plate size BGI (P = 0.32). More patients in the MGI group needed secondary operative management (11%, P = 0.03). CONCLUSIONS: The MGI was noninferior to the BGI in lowering IOP. Differences in time until device failure, VA outcomes, and medication use were inconclusive. The MGI required more secondary operative interventions. The MGI required less time to implant than the BGI's 350 mm2 plate size implant. Overall, the use of both GDDs is justifiable to lower IOP when more conservative management has failed.