Subconjunctival Administration of an Adeno-Associated Virus Expressing Stanniocalcin-1 Provides Sustained Intraocular Pressure Reduction in Mice.

Purpose: To investigate subconjunctival administration of a single-stranded, adeno-associated virus, serotype 2, engineered to express stanniocalcin-1 with a FLAG tag (ssAAV2-STC-1-FLAG) as a novel sustained (IOP) lowering agent with a reduced ocular surface side effect profile. Design: In vivo preclinical investigation in mice. Subjects: C57BL/6J, DBA/2J, prostaglandin F (FP) receptor knockout mice. Methods: Normotensive C57BL/6J mice were treated with a subconjunctival injection of ssAAV2-STC-1-FLAG (2 µL; 6 × 109 viral genomes [VGs]) in 1 eye and the same volume and concentration of ssAAV2-green fluorescent protein (GFP) or the same volume of phosphate-buffered saline in the fellow eye. Ocular hypertensive DBA/2J mice were subconjunctivally injected with 6 × 109 VGs of ssAAV2-STC-1-FLAG or ssAAV2-GFP. Steroid-mediated ocular hypertension was induced in C57BL/6J mice with weekly injections of dexamethasone into the conjunctival fornix, and mice were then injected subconjunctivally with 6 × 109 VGs of ssAAV2-STC-1-FLAG or ssAAV2-GFP. Prostaglandin F receptor knockout mice were injected subconjunctivally with 6 × 109 VGs of ssAAV2-STC-1-FLAG or phosphate-buffered saline. An identical vector was constructed without the FLAG tag (ssAAV2-STC-1) and evaluated in normotensive C57BL/6J mice. Intraocular pressure was assessed using the Tonolab tonometer for all experiments. Tumor necrosis factor alpha (TNFα), a marker of ocular surface inflammation, was compared between subconjunctivally delivered ssAAV2-STC-1-FLAG and other treatments including daily topical latanoprost. Main Outcome Measures: Intraocular pressure assessment. Results: Subconjunctival delivery of ssAAV2-STC-1-FLAG significantly reduced IOP for 10 weeks post injection in normotensive mice. Maximal IOP reduction was seen at week 3 postinjection (17.4%; 17.1 ± 0.8 vs. 14.1 ± 0.8 mmHg, P < 0.001). After the IOP-lowering effect had waned, a second injection restored the ocular hypotensive effect. Subconjunctivally delivered ssAAV2-STC-1-FLAG lowered IOP in DBA/2J mice (16.9%; 17.8 ± 2.0 vs. 14.8 ± 0.9 mmHg, P < 0.001) and steroid-mediated ocular hypertensive mice (20.0%; 19.0 ± 0.6 vs. 15.2 ± 0.7 mmHg, P < 0.001) over the experimental period. This construct also reduced IOP to a similar extent in wild-type (15.9%) and FP receptor knockout (15.7%) mice compared with the fellow eye. A related construct also lowered IOP without the FLAG tag in a similar manner. Reduction in conjunctival TNFα was seen when comparing subconjunctivally delivered ssAAV2-STC-1-FLAG to daily topical latanoprost. Conclusions: Subconjunctival delivery of the STC-1 transgene with a vector system may represent a novel treatment strategy for sustained IOP reduction and improved ocular tolerability that also avoids the daily dosing requirements of currently available medications. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Progressive Paracentral Visual Field Loss at Low Intraocular Pressures Following LASIK.

Intraocular pressure is currently the only known reliable, modifiable risk factor for the development and progression of glaucoma. Other risk factors for glaucoma include increasing age, myopia, decreased central corneal thickness, and low corneal hysteresis (CH) measurements. Photoablative keratorefractive surgery including laser assisted in situ keratomileusis (LASIK) has become a common way to treat refractive error, with over 25 million procedures performed in the United States alone. Though myopic LASIK has been associated with a decrease in CH measurements, relatively little is known about the risk of LASIK on glaucoma onset and progression. Here we present an observational study of 4 consecutive relatively young and otherwise healthy glaucoma patients with a history of myopic LASIK who showed progression of paracentral visual field deficits at intraocular pressures of 12 mm Hg or less while being carefully monitored. Therefore, these patients required lower targets of intraocular pressure, in the single-digit range, to slow or halt progression. In this cohort, the average corneal hysteresis was more than 2 standard deviations below normal values. This series suggests that additional study into the association of LASIK and glaucoma is warranted, including the potential risk contribution of diminished CH. These studies may be particularly relevant as patients who underwent LASIK procedures in the early 2000s may now be at increased risk of glaucoma due to the risk factor of age.

Appropriateness of Ophthalmology Recommendations From an Online Chat-Based Artificial Intelligence Model.

Objective: To determine the appropriateness of ophthalmology recommendations from an online chat-based artificial intelligence model to ophthalmology questions. Patients and Methods: Cross-sectional qualitative study from April 1, 2023, to April 30, 2023. A total of 192 questions were generated spanning all ophthalmic subspecialties. Each question was posed to a large language model (LLM) 3 times. The responses were graded by appropriate subspecialists as appropriate, inappropriate, or unreliable in 2 grading contexts. The first grading context was if the information was presented on a patient information site. The second was an LLM-generated draft response to patient queries sent by the electronic medical record (EMR). Appropriate was defined as accurate and specific enough to serve as a surrogate for physician-approved information. Main outcome measure was percentage of appropriate responses per subspecialty. Results: For patient information site-related questions, the LLM provided an overall average of 79% appropriate responses. Variable rates of average appropriateness were observed across ophthalmic subspecialties for patient information site information ranging from 56% to 100%: cataract or refractive (92%), cornea (56%), glaucoma (72%), neuro-ophthalmology (67%), oculoplastic or orbital surgery (80%), ocular oncology (100%), pediatrics (89%), vitreoretinal diseases (86%), and uveitis (65%). For draft responses to patient questions via EMR, the LLM provided an overall average of 74% appropriate responses and varied by subspecialty: cataract or refractive (85%), cornea (54%), glaucoma (77%), neuro-ophthalmology (63%), oculoplastic or orbital surgery (62%), ocular oncology (90%), pediatrics (94%), vitreoretinal diseases (88%), and uveitis (55%). Stratifying grades across health information categories (disease and condition, risk and prevention, surgery-related, and treatment and management) showed notable but insignificant variations, with disease and condition often rated highest (72% and 69%) for appropriateness and surgery-related (55% and 51%) lowest, in both contexts. Conclusion: This LLM reported mostly appropriate responses across multiple ophthalmology subspecialties in the context of both patient information sites and EMR-related responses to patient questions. Current LLM offerings require optimization and improvement before widespread clinical use.

Permanent ocular remodeling in the setting of chronic hypotony after trabeculectomy: A case report.

Purpose: Trabeculectomy surgery is a commonly performed procedure for treatment of glaucoma. While the goal is to lower intraocular pressure, over-filtration may cause hypotony with ocular structural changes and vision loss. Observations: A 53-year-old woman with primary open-angle glaucoma was referred to our service for further evaluation. The patient previously underwent trabeculectomy 9 years prior and was found to have a cataract and hypotony maculopathy in the right eye. Treatment options included cataract surgery alone, bleb revision alone, or combined cataract extraction and bleb revision. Biometry revealed corneal astigmatism in the right eye, and significant disparity in axial length between the two eyes. Since the axial length and corneal astigmatic changes were presumed to be at least partially reversible, measurements from the non-operative left eye influenced the lens selection for the hypotonous right eye. The patient underwent combined phacoemulsification and bleb revision. While IOP increased and hypotony was partly reversed, there was hyperopic and astigmatic refractive surprise after surgery.The patient subsequently underwent intraocular lens exchange using biometric values of the previously hypotonous eye and met the target post-operative refractive goal. Conclusions and importance: This case demonstrates changes to the axial length and ocular structure following longstanding hypotony maculopathy may be permanent, even after restoration of normotensive intraocular pressure.

Single-Use Lens Compromise During Selective Laser Trabeculoplasty.

PRCIS: Damage to disposable selective laser trabeculoplasty (SLT) lenses correlated with the amount of total laser energy. Furthermore, greater lens damage was associated with diminished patient treatment response. PURPOSE: Disposable SLT lenses have been observed to be damaged during use by laser, potentially affecting therapeutic response. This study sought to identify factors associated with the magnitude of lens damage and its effect on treatment outcomes. PATIENT AND METHODS: We analyzed 113 eyes from 82 patients who underwent SLT between 2020 and 2021 at an American academic medical center. For each procedure, we recorded baseline patient characteristics, procedure settings, physician age (as a possible factor causing laser defocus due to accommodation), and area of lens damage. Treatment response was calculated as the difference between preoperative and postoperative intraocular pressure (IOP). RESULTS: Area of lens damage was associated with greater total laser energy ( r =0.34, P <0.001) and greater mean energy per application ( r =0.37, P <0.001). IOP reduction decreased with increasing lens damage ( r =-0.19, P =0.022). Lens damage was not associated with patient characteristics indicative of glaucoma severity or user settings (physician age and slit lamp used). Greater IOP reduction was associated with higher preop IOP ( r =0.46, P <0.001) and a smaller cup-to-disc ratio ( r =0.22, P =0.036). IOP reduction was not associated with retinal nerve fiber layer thickness, patient age, or the number of glaucoma medications. CONCLUSIONS: Increased laser damage to disposable SLT lenses was associated with diminished treatment effect. The amount of damage was correlated with total and average laser energy, but not patient or physician factors. Overall, these findings call for reconsideration of using disposable SLT lenses as part of routine practice.

Efficacy of Selective Laser Trabeculoplasty in Patients on Systemic Immunosuppressive Therapy.

PRCIS: 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.

Metabolic syndrome and its components are associated with non-arteritic anterior ischaemic optic neuropathy.

PURPOSE: To determine whether metabolic syndrome (MetS) is a risk factor for various forms of optic neuropathy including non-arteritic anterior ischaemic optic neuropathy (NAION). METHODS: This population-based analysis identified patients ≥40 years of age in Olmsted County, Minnesota, USA using the Rochester Epidemiology Project 2005-2018. Patients with MetS were identified if three or more of the five standard criteria for diagnosing MetS were present: systemic hypertension, hyperglycaemia, hypertriglyceridaemia, reduced high-density lipoprotein cholesterol (hypoalphalipoproteinaemia) and central adiposity defined by increased body mass index. Charts of patients identified as having an optic neuropathy were reviewed to record specific diagnoses and compared with patients without ocular pathology other than cataract. The odds ratio (OR) of association with MetS was calculated and adjusted for age, sex and race with multivariate analysis for the various optic neuropathies. RESULTS: Patients with MetS were more likely to have an optic neuropathy than those without (OR 2.2, p<0.001). After adjusting for age, sex and race, the only optic neuropathy found to be significantly associated with MetS was NAION (OR 6.17, p=0.002). For patients with NAION, though each individual component of MetS was individually significantly associated with MetS, further analysis suggested that hypertriglyceridaemia, hypoalphalipoproteinaemia and hyperglycaemia were likely the key drivers in the overall significance between NAION and MetS. CONCLUSION: Patients with MetS were more likely to have NAION. Further studies are needed to determine whether MetS is a modifiable risk factor for NAION.

Optic Disc Drusen in Patients With Ocular Hypertension: A Case Series and Review of the Literature.

BACKGROUND: The identification of glaucomatous optic neuropathy in the setting of optic disc drusen (ODD) is a challenge, and the decision of whether to offer treatment in the form of intraocular pressure (IOP) reduction is controversial. Here, we present a series of patients with coexisting ocular hypertension and ODD to evaluate clinical features, treatment options, and progression of optic neuropathy. In addition, a review of the literature on ODD with elevated IOP is provided. METHODS: Six patients with ODD and a history of ocular hypertension are presented. Components of the examination and imaging modalities used to establish the diagnosis of ODD were recorded and a description of ocular hypertension history, glaucoma testing, and the potential treatment of IOP were also provided. RESULTS: In this series, 4 of 6 patients with concurrent ocular hypertension and ODD showed progression of optic neuropathy as assessed by visual field or retinal nerve fiber layer thickness. Of the 2 patients who did not show evidence of progression, 1 was treated with IOP-lowering medications and 1 was observed off treatment. Of the 4 patients who showed evidence of progression, all 4 were initially treated with IOP-lowering medications and 2 ultimately went on to have trabeculectomy surgery. In the patients with progressive optic neuropathy, lowering the IOP seemed to halt the progression suggesting there was a pressure-sensitive component. CONCLUSIONS: Distinguishing changes to the optic nerve, particularly the structural changes at the lamina cribrosa of true glaucomatous optic neuropathy in the setting of ODD, is a challenge. Careful consideration of risk factors including age, presenting features, progression indicators, and management goals is to be accounted for in the decision to offer treatment. We see the presence ODD in the patients with ocular hypertension as an additional risk for progressive changes to the nerve fiber layer and visual field that needs to be considered when determining whether to initiate therapy. Our data suggest that treatment of IOP in the patients with ocular hypertension with ODD and evidence of progression reduces the risk of further progression. Further work is needed to determine whether progression of optic neuropathy in the setting of coexisting ODD and ocular hypertension is related mechanistically to predominantly an ODD-type process, a glaucomatous process, or a combination thereof.

Surgical Advancement of Tenon's Layer During Trabeculectomy Improves Bleb Morphology.

Trabeculectomy surgery remains the gold standard incisional glaucoma surgical procedure in many practices, particularly for patients requiring intraocular pressure (IOP) in the low teens or below. However, trabeculectomy surgery is associated with complications including leakage, over filtration, or fibrosis of the surgical bleb. Morphology of the surgical bleb is an important predictor of surgical success defined as long-term IOP reduction with minimal to no complications. There have been many, often subtle, variations in the surgical technique in hopes of improving long-term IOP reduction. However, fewer changes have been implemented specifically to modify bleb morphology. In our surgical practice, we began performing a thorough dissection and advancement of Tenon's layer with incorporation into the conjunctival closure in a 2-layered manner. This technique allowed flow of aqueous to a delineated potential space between sclera and Tenon's layer. Our clinical observations were improved bleb morphology characterized by diffuse, low-lying blebs with nonischemic overlying conjunctiva compared with those performed with a more traditional trabeculectomy technique. Since we incorporated this change into our practice at a defined time, we have a small number of patients in our practice that had a more traditional trabeculectomy technique in the fellow eye. Therefore, in our surgical practice, a small number of patients had trabeculectomy in 1 eye before implementation of this new technique, and then had trabeculectomy in the fellow eye after this technique was adopted, providing opportunity for comparison of bleb morphology with and without Tenon advancement. In series we present two representative, index cases and describe our surgical technique.

Transgene expression of Stanniocalcin-1 provides sustained intraocular pressure reduction by increasing outflow facility.

Glaucoma is the leading cause of irreversible blindness worldwide. Therapies for glaucoma are directed toward reducing intraocular pressure (IOP), the leading risk factor and only reliable therapeutic target via topical medications or with procedural intervention including laser or surgery. Though topical therapeutics are typically first line, less than 50% of patients take drops as prescribed. Sustained release technologies that decrease IOP for extended periods of time are being examined for clinical use. We recently identified Stanniocalcin-1, a naturally occurring hormone, as an IOP-lowering agent. Here, we show that a single injection into the anterior chamber of mice with an adeno-associated viral vector containing the transgene of stanniocalcin-1 results in diffuse and sustained expression of the protein and produces IOP reduction for up to 6 months. As the treatment effect begins to wane, IOP-lowering can be rescued with a repeat injection. Aqueous humor dynamic studies revealed an increase in outflow facility as the mechanism of action. This first-in-class therapeutic approach has the potential to improve care and reduce the rates of vision loss in the 80 million people worldwide currently affected by glaucoma.

Angle closure secondary to lens remnants in a patient with presumed aphakia: case report.

BACKGROUND: Eyes with a short axial length or anterior chamber depth often develop narrowed anterior chamber angles in association with an enlarging crystalline lens. We report a case of a patient who presented in angle closure, with a distant history of prior intervention for congenital cataracts and was presumed to be aphakic. CASE PRESENTATION: A 78-year-old male presented with acute onset unilateral eye pain and blurred vision. He was found to have increased intraocular pressure, anteriorly bowed iris, and angle closure. Despite prior documentation of aphakia after treatment for congenital cataracts, detailed workup revealed residual crystalline lens material pushing the peripheral iris anteriorly. Further history confirmed that the patient underwent a procedure in the 1940's to remove lens material centrally but was not truly aphakic. The patient was treated with anterior chamber paracentesis and intraocular pressure lowering drops. His intraocular pressure remains controlled with medical therapy alone. CONCLUSIONS: Patients that appear to be aphakic centrally may still present with angle closure secondary to residual peripheral lens material. This case highlights the importance of keeping this etiology on the differential in a patient with presumed aphakia.

Intravitreal Administration of Stanniocalcin-1 Rescues Photoreceptor Degeneration with Reduced Oxidative Stress and Inflammation in a Porcine Model of Retinitis Pigmentosa.

PURPOSE: To investigate the effect of stanniocalcin-1 (STC-1), a secreted polypeptide exhibiting multiple functions in cell survival and death, on photoreceptor degeneration in a porcine model of retinitis pigmentosa (RP). METHODS: P23H transgenic pigs (TG P23H) and wild-type hybrid littermates were obtained from the National Swine Resource and Research Center. Human recombinant STC-1 was injected intravitreally every 2 weeks from postnatal day 15 (P15) to P75. The contralateral eye was injected with balanced salt solution as a control. Electroretinography (ERG) and spectral domain optical coherence tomography (SD-OCT) were performed to evaluate retinal function and morphology in vivo at P90. Retinal tissue was collected for histologic analysis and molecular assays to evaluate the antioxidative and anti-inflammatory mechanisms by which STC-1 may rescue photoreceptor degeneration. RESULTS: Intravitreal injection of STC-1 improved retinal function in TG P23H pigs with increased photopic and flicker ERG a- and b-wave amplitudes. Greater integrity of the ellipsoid zone (EZ) band on SD-OCT and morphologic rescue with preservation of cone photoreceptors were observed in STC-1-treated TG P23H pigs. STC-1 altered gene expression in TG P23H pig retina on microarray analysis and increased photoreceptor specific gene expression by reverse transcription-polymerase chain reaction analysis. STC-1 significantly decreased oxidative stress and the expressions of NLRP3 inflammasome, cleaved caspase-1, and IL-1ß in TG P23H pig retina. CONCLUSIONS: Intravitreal administration of STC-1 enhances cone photoreceptor function, improves EZ integrity, and reduces retinal degeneration through antioxidative and anti-inflammatory effects in a large animal (pig) model of the most common form of autosomal dominant RP in the United States.

Effect of ATP-sensitive Potassium Channel Openers on Intraocular Pressure in Ocular Hypertensive Animal Models.

Purpose: To evaluate the effect of ATP-sensitive potassium channel openers cromakalim prodrug 1 (CKLP1) and diazoxide on IOP in three independent mouse models of ocular hypertension. Methods: Baseline IOP was measured in TGFß2 overexpression, steroid-induced, and iris dispersion (DBA/2J) ocular hypertension mouse models, followed by once daily eyedrop administration with CKLP1 (5 mM) or diazoxide (5 mM). The IOP was measured in conscious animals with a handheld rebound tonometer. Aqueous humor dynamics were assessed by a constant perfusion method. Effect of treatment on ocular tissues was evaluated by transmission electron microscopy. Results: CKLP1 decreased the IOP by 20% in TGFß2 overexpressing mice (n = 6; P < 0.0001), 24% in steroid-induced ocular hypertensive mice (n = 8; P < 0.0001), and 43% in DBA/2J mice (n = 15; P < 0.0001). Diazoxide decreased the IOP by 32% in mice with steroid-induced ocular hypertension (n = 13; P < 0.0001) and by 41% in DBA/2J mice (n = 4; P = 0.005). An analysis of the aqueous humor dynamics revealed that CKLP1 decreased the episcleral venous pressure by 29% in TGFß2 overexpressing mice (n = 13; P < 0.0001) and by 72% in DBA/2J mice (n = 4 control, 3 treated; P = 0.0002). Diazoxide lowered episcleral venous pressure by 35% in steroid-induced ocular hypertensive mice (n = 3; P = 0.03). Tissue histology and cell morphology appeared normal when compared with controls. Accumulation of extracellular matrix was reduced in CKLP1- and diazoxide-treated eyes in the steroid-induced ocular hypertension model. Conclusions: ATP-sensitive potassium channel openers CKLP1 and diazoxide effectively decreased the IOP in ocular hypertensive animal models by decreasing the episcleral venous pressure, supporting a potential therapeutic application of these agents in ocular hypertension and glaucoma.

Association of Metabolic Syndrome With Glaucoma and Ocular Hypertension in a Midwest United States Population.

PRCIS: For patients with glaucoma, metabolic syndrome was associated with higher intraocular pressure and greater central corneal thickness. Patients with metabolic syndrome were more likely to have ocular hypertension. PURPOSE: The purpose of this study was to determine whether glaucomatous optic neuropathy, also known as glaucoma, and ocular hypertension are more likely to occur in patients with metabolic syndrome. PATIENTS AND METHODS: Patients in Olmsted County, MN, were identified as having metabolic syndrome based on diagnosis codes, laboratory values, and/or medication use to meet 3 or more of the 5 standard criteria for diagnosing metabolic syndrome: systemic hypertension, hyperglycemia, hypertriglyceridemia, reduced high-density lipoprotein cholesterol, and central adiposity defined by increased body mass index. Patients with glaucoma, including primary open angle, low tension, pigment dispersion, and pseudoexfoliation, were identified using diagnostic codes. The charts of patients with glaucoma were individually reviewed to collect visual acuity, intraocular pressure, cup to disc ratio, central corneal thickness, visual field mean deviation, retinal nerve fiber layer thickness, and treatment of intraocular pressure. Patients with ocular hypertension were separately identified and similarly evaluated. RESULTS: For patients with glaucoma, those with metabolic syndrome had higher intraocular pressure and greater central corneal thickness compared with those without metabolic syndrome. After adjustment for central corneal thickness, there was no longer a significant difference in intraocular pressure between groups. Metabolic syndrome was also associated with the diagnosis of ocular hypertension, and although central corneal thickness trended higher in patients with metabolic syndrome, it did not attain statistical significance. CONCLUSION: In Olmsted County, though metabolic syndrome was associated with ocular hypertension and higher intraocular pressure in patients with glaucoma, the results were likely related to a thicker central corneal in this patient population.

Postradiation Optic Atrophy Is Associated With Intraocular Pressure and May Manifest With Neuroretinal Rim Thinning.

BACKGROUND: To determine risk factors for postradiation optic atrophy (PROA) after plaque radiotherapy for uveal melanoma. METHODS: A single center, retrospective cohort study of patients diagnosed with uveal melanoma involving choroid and/or ciliary body treated with plaque between January 1, 2008, and December 31, 2016. Outcomes included development of PROA with pallor alone or with concomitant neuroretinal rim thinning (NRT). Cox regression analysis was performed to identify risk factors for PROA. RESULTS: Of 78 plaque-irradiated patients, PROA developed in 41 (53%), with concomitant NRT in 15 (19%). Risk factors for PROA of any type included presentation with worse visual acuity (odds ratio [95% confidence interval] 5.6 [2.3-14.1], P < 0.001), higher baseline intraocular pressure (IOP; 14 vs 16 mm Hg) (1.1 [1.0-1.2], P = 0.03), shorter tumor distance to optic disc (1.3 [1.2-1.5], P < 0.001) and foveola (1.2 [1.1-1.3], P < 0.001), subfoveal subretinal fluid (3.8 [2.0-7.1], P < 0.001), greater radiation prescription depth (1.3 [1.1-1.6], P = 0.002), dose to fovea (point dose) (1.01 [1.01-1.02], P < 0.001), and mean (1.02 [1.02-1.03], P < 0.001) and maximum dose to optic disc per 1 Gy increase (1.02 [1.01-1.03], P < 0.001). On multivariate modeling, dose to disc, baseline IOP, and subfoveal fluid remained significant. Subanalysis revealed risk factors for pallor with NRT of greater mean radiation dose to disc (1.03 [1.01-1.05], P = 0.003), higher maximum IOP (17 vs 20 mm Hg) (1.4 [1.2-1.7], P < 0.001), and subfoveal fluid (12 [2-63], P = 0.004). CONCLUSION: PROA may result in NRT in addition to optic disc pallor. Risk factors for PROA included higher radiation dose to optic disc, higher baseline IOP, and subfoveal fluid. Higher maximum IOP contributed to concomitant NRT.

Multiple Systemic Vascular Risk Factors Are Associated With Low-Tension Glaucoma.

PRCIS: Multiple systemic vascular-associated conditions including systemic hypertension and hypotension, diabetes mellitus, migraine headache, peripheral vascular disease, Raynaud syndrome, and anemia were associated with low-tension glaucoma. PURPOSE: The purpose of this study was to identify systemic risk factors associated with low-tension glaucoma. PATIENTS AND METHODS: A retrospective case-control study design was employed to identify patients seen at the Mayo Clinic Department of Ophthalmology between 2005 and 2015 with low-tension glaucoma and an age-matched and sex-matched control group, each containing 277 patients. RESULTS: The low-tension glaucoma group had more myopic refractive errors (-1.6 vs. -1.0 D, P<0.001), lower intraocular pressure (14.2 vs. 15.2 mm Hg, P<0.001), and a higher cup-to-disc ratio (0.7 vs. 0.3, P<0.001). The low-tension glaucoma group was significantly less likely to be obese (body mass index >30, P=0.03). This group had a significantly higher prevalence of systemic hypertension [odds ratio (OR): 1.64, P=0.004], diabetes mellitus (OR: 3.01, P<0.001), peripheral vascular disease (OR: 2.61, P=0.009), migraine headache (OR: 2.12, P=0.02), anemia (OR: 2.18, P=0.003), systemic hypotension (OR: 4.43, P<0.001), Raynaud syndrome (OR: 3.09, P=0.05), and angiotensin-converting enzyme inhibitor (OR: 1.64, P=0.01) or calcium channel blocker use (OR: 1.98, P=0.004). After adjusting for systemic hypertension, calcium channel blocker use remained significant (OR: 1.70, P=0.03). No significant difference was found between groups with respect to hyperlipidemia, obstructive sleep apnea, coronary artery disease, carotid stenosis, stroke, or statin, angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, beta-blocker, or metformin use. CONCLUSIONS: Multiple vascular-associated conditions were associated with low-tension glaucoma including systemic hypertension, diabetes mellitus, peripheral vascular disease, migraine headache, Raynaud syndrome, anemia, systemic hypotension, and calcium channel blocker use. This study strengthens the evidence for the vascular hypothesis of low-tension glaucoma.

Efficacy and safety of blepharoptosis repair after incisional glaucoma surgery.

PURPOSE: There is an increased risk for development of blepharoptosis after incisional glaucoma surgery. Data on safety and efficacy of ptosis repair in this group of patients in limited. The goal of this study is to evaluate outcomes and identify potential risk factors for failure of ptosis repair in eyes with history of incisional glaucoma surgery. METHODS: A retrospective chart review was performed of all patients who underwent incisional glaucoma surgery, specifically trabeculectomy or implantation of glaucoma drainage device (GDD), and subsequent ptosis repair at a single institution from 2009 to 2019. Ptosis surgery outcomes were compared to a control group who underwent ptosis repair after cataract surgery. RESULTS: Seventy-eight eyes of 64 patients were included in the glaucoma surgery group. The rate of severe ptosis (margin reflex distance 1 ⩽ 0 mm) among glaucoma surgery patients was higher compared to control (35 of 78 (44.9%) vs 23 of 82 (28.6%). Ptosis repair was successful in 59 of 78 eyes (75.6%), which was similar to control. Risk for revision surgery was increased more than five-fold in the GDD group compared to control. There were no cases of early or late bleb-related complications. CONCLUSIONS: Ptosis repair can be performed safely in patients after incisional glaucoma surgery. Müller muscle conjunctival resection and external levator advancement are equally effective. Patients with history of GDD should be advised about the potentially increased risk of need for revision surgery.

Rates of Diplopia in Ahmed FP7, Baerveldt 250, and 350 Glaucoma Patients Compared With Medical Controls.

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.