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.

Central Visual Field Testing in Early Glaucoma: A Report by the American Academy of Ophthalmology.

PURPOSE: To evaluate the current published literature on the utility of the 10-2 visual field (VF) testing strategy for the evaluation and management of early glaucoma, defined here as mean deviation (MD) better than -6 decibels (dB). METHODS: A search of the peer-reviewed literature was last conducted in June 2023 in the PubMed database. Abstracts of 986 articles were examined to exclude reviews and non-English-language articles. After inclusion and exclusion criteria were applied, 26 articles were selected, and the panel methodologist rated them for strength of evidence. Thirteen articles were rated level I, and 8 articles were rated level II. The 5 level III articles were excluded. Data from the 21 included articles were abstracted and reviewed. RESULTS: The central 12 locations on the 24-2 VF test grid lie within the central 10 degrees covered by the 10-2 VF test. In early glaucoma, defects detected within the central 10 degrees generally agree between the 2 tests. Defects within the central 10 degrees of the 24-2 VF test can predict defects on the 10-2 VF test, although the 24-2 may miss defects detected on the 10-2 VF test. In addition, results from the 10-2 VF test show better association with findings from OCT scans of the macular ganglion cell complex. Modifications of the 24-2 test that include extra test locations within the central 10 degrees improve detection of central defects found on 10-2 VF testing. CONCLUSIONS: Evidence to date does not support routine testing using 10-2 VF for patients with early glaucoma. However, early 10-2 VF testing may provide sufficient additional information for some patients, particularly those with a repeatable defect within the central 12 locations of the standard 24-2 VF test or who have inner retinal layer thinning on OCT scans of the macula. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Aqueous Shunts with Extraocular Reservoir for Open-Angle Adult Glaucoma: A Report by the American Academy of Ophthalmology.

PURPOSE: To evaluate the recently published literature on the efficacy and safety of the use of aqueous shunts with extraocular reservoir for the management of adult open-angle glaucomas (OAGs). METHODS: A search of peer-reviewed literature was last conducted in April 2023 of the PubMed database and included only articles published since the last aqueous shunt Ophthalmic Technology Assessment, which assessed articles published before 2008. The abstracts of these 419 articles were examined, and 58 studies were selected for full-text analysis. After inclusion and exclusion criteria were applied, 28 articles were selected and assigned ratings by the panel methodologist according to the level of evidence. Twenty-five articles were rated level I and 3 articles were rated level II. There were no level III articles. RESULTS: Implantation of aqueous shunts with extraocular reservoir can lower intraocular pressure (IOP) by between one-third and one-half of baseline IOP, depending on whether it is undertaken as the primary or secondary glaucoma surgery. Success rates for aqueous shunts were found to be better than for trabeculectomies in eyes with prior incisional surgery. Conversely, in eyes without prior incisional surgery, implantation of aqueous shunts was found to have an overall lower success rate as the primary glaucoma procedure compared with trabeculectomy. Although both valved and nonvalved aqueous shunts with extraocular reservoir were effective, the nonvalved device generally achieved slightly lower long-term IOPs with fewer glaucoma medications and less need for additional glaucoma surgery. Both devices slow the rates of visual field progression with efficacy comparable with that of trabeculectomy. Early aqueous humor suppression after aqueous shunt implantation is recommended for the management of the postoperative hypertensive phase and long-term IOP control. No strong evidence supports the routine use of mitomycin C with aqueous shunt implantation for OAG. CONCLUSIONS: Implantation of aqueous shunts with extraocular reservoir, including valved or nonvalved devices, has been shown to be an effective strategy to lower IOP. Strong level I evidence supports the use of aqueous shunts with extraocular reservoir by clinicians for the management of adult OAG. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Trabecular Procedures Combined with Cataract Surgery for Open-Angle Glaucoma: A Report by the American Academy of Ophthalmology.

PURPOSE: To determine the intraocular pressure (IOP) reduction of various trabecular procedures (a form of minimally invasive glaucoma surgery [MIGS]) combined with cataract surgery compared with cataract surgery alone, to compare the safety of the various trabecular procedures, and to highlight patient characteristics that may favor one trabecular procedure over another. METHODS: A search of English-language peer-reviewed literature in the PubMed database was initially conducted in February 2021 and updated in April 2023. This yielded 279 articles. Twenty studies met initial inclusion and exclusion criteria and were assessed for quality by the panel methodologist. Of these, 10 were rated level I, 3 were rated level II, and 7 were rated level III. Only the 10 level I randomized controlled trials (RCTs) were included in this assessment, and all were subject to potential industry-sponsorship bias. RESULTS: The current analysis focuses on the amount of IOP reduction (in studies that involved medication washout) and on IOP reduction with concurrent medication reduction (in studies that did not involve medication washout). Based on studies that performed a medication washout, adding a trabecular procedure to cataract surgery provided an additional 1.6 to 2.3 mmHg IOP reduction in subjects with hypertensive, mild to moderate open-angle glaucoma (OAG) at 2 years over cataract surgery alone, which itself provided approximately 5.4 to 7.6 mmHg IOP reduction. In other words, adding a trabecular procedure provided an additional 3.8% to 8.9% IOP reduction over cataract surgery alone, which itself provided 21% to 28% IOP reduction. There was no clear benefit of one trabecular procedure over another. Patient-specific considerations that can guide procedure selection include uveitis predisposition, bleeding risk, metal allergy, and narrowing of Schlemm's canal. There are no level I data on the efficacy of trabecular procedures in subjects with pretreatment IOP of 21 mmHg or less. CONCLUSIONS: Trabecular procedures combined with cataract surgery provide an additional mild IOP reduction over cataract surgery alone in hypertensive OAG subjects. Additional research should standardize outcome definitions, avoid industry sponsorship bias, and study the efficacy of these procedures in normotensive OAG. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Determination of the Trans-Lamina Cribrosa Pressure Difference in a Community-Based Population and its Association with Open-Angle Glaucoma.

PURPOSE: To determine the trans-lamina cribrosa pressure difference (TLCPD) in a cohort of normal community-based patients and the relationship to primary open-angle glaucoma (POAG) and normal-tension glaucoma (NTG). DESIGN: Retrospective cohort study of the Mayo Clinic Study of Aging. PARTICIPANTS: The Mayo Clinic Study of Aging is a prospective study evaluating the normal aging population. METHODS: Mayo Clinic Study of Aging patients who underwent routine lumbar puncture (LP) studies with eye examinations were reviewed. The trans-lamina cribrosa pressure difference was calculated in 2 contexts of intraocular pressure (IOP): (1) maximum IOP at eye visit closest in time to the LP (closest-in-time TLCPD); and (2) IOP before IOP-lowering treatment (pretreatment IOP and pretreatment TLCPD) in POAG and NTG patients. Glaucoma patients without POAG or NTG were excluded. Regression analyses were performed to determine the relationship with glaucoma. MAIN OUTCOME MEASURES: IOP, intracranial pressure, TLCPD, POAG, normal-tension glaucoma (NTG) diagnosis, glaucoma parameters. RESULTS: Five hundred forty-eight patients were analyzed. Of these, there were 38 treated glaucoma patients (14 POAG and 24 NTG) and 510 nonglaucomatous patients. Cerebral spinal fluid (CSF) opening pressure was 155.0 ± 42.2 mmH2O in nonglaucomatous patients, 144.0 ± 34.0 mmH2O in POAG (P = 0.15 vs. nonglaucomatous patients), and 136.6 ± 29.3 mmH2O in NTG (P = 0.017 vs. nonglaucomatous patients). Intraocular pressure was 15.47 ± 2.9 mmHg in nonglaucomatous patients, 26.6 ± 3.7 mmHg in POAG, and 17.4 ± 3.4 mmHg in NTG. The closest-in-time TLCPD in the nonglaucomatous cohort was 4.07 ± 4.22 mmHg, which was lower than both the POAG cohort (7.19 ± 3.6 mmHg) and the NTG cohort (5.79 ± 4.5 mmHg, P = 0.04). Pretreatment TLCPD for the overall glaucoma cohort was 10.57 ± 6.1 mmHg. The POAG cohort had a higher pretreatment TLCPD (16.05 ± 5.2 mmHg) than the NTG cohort (7.37 ± 4.1 mmHg; P < 0.0001). Closest-in-time TLCPD for the nonglaucoma cohort (4.07± 4.2 mmHg) was significantly lower than pretreatment TLCPDs for both POAG (16.05 ± 5.2 mmHg; P < 0.0001) and NTG (7.37 ± 4.1 mmHg; P < 0.0001) cohorts. CONCLUSIONS: This study establishes the baseline TLCPD in a large cohort of normal, community-based patients. The differences in regression analysis between TLCPD and IOP suggests NTG pathophysiology is partially driven by TLCPD, but is also likely multifactorial. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

The Effect of Scleral Buckle Surgery on Tonographic Outflow Facility, Positional Intraocular Pressure, and Ocular Biomechanics.

PURPOSE: To investigate the in vivo effect of scleral buckle surgery on ocular biomechanics and aqueous humor dynamics. DESIGN: Prospective observational cross-sectional study. PARTICIPANTS: Nine patients with unilateral 360 degree encircling scleral buckles without vitrectomy for rhegmatogenous retinal detachments, between 3 and 39 months postoperative. METHODS: All measurements were performed in both eyes of all participants. Intraocular pressure (IOP) was measured in the seated and supine positions using pneumatonometry. Outflow facility was measured using 2-minute weighted pneumatonography. Ocular rigidity coefficient was determined from the Friedenwald equations based on the difference in IOP with and without a weighted tonometer tip. The percentage change in IOP upon transitioning from seated to supine was calculated. Measurements for buckled and nonbuckled eyes were compared using paired Student t test of means. MAIN OUTCOME MEASURES: Sitting and supine IOP and percentage difference between the 2 positions; outflow facility; ocular rigidity coefficient. RESULTS: Seated IOP was similar between buckled and nonbuckled eyes (16.1 ± 2.5 vs. 16.7 ± 2.7 mmHg; P = 0.5) whereas supine IOP was lower in buckled eyes compared with nonbuckled eyes (18.7 ± 2.6 vs. 21.3 ± 2.5 mmHg; P = 0.008). The percentage increase in IOP upon change in body position from seated to supine was greater in nonbuckled eyes (17.4 ± 9.4% vs. 27.6 ± 9.5%; P = 0.005). Ocular rigidity coefficient was lower in buckled (9.9 × 10-3 ± 1.4 × 10-3 µL-1) vs. nonbuckled eyes (14.4 × 10-3 ± 3.1 × 10-3 µL-1; P = 0.006). Outflow facility was not significantly different in buckled and nonbuckled eyes. CONCLUSIONS: Scleral buckling decreases ocular rigidity but does not affect outflow facility. This change in ocular biomechanics likely results in the attenuated IOP change from seated to supine position. Decreased ocular rigidity may also reduce IOP fluctuations and potentially reduce the risk for glaucoma progression. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Selective Laser Trabeculoplasty for the Treatment of Glaucoma: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the current published literature for high-quality studies on the use of selective laser trabeculoplasty (SLT) for the treatment of glaucoma. This is an update of the Ophthalmic Technology Assessment titled, "Laser Trabeculoplasty for Open-Angle Glaucoma," published in November 2011. METHODS: Literature searches in the PubMed database in March 2020, September 2021, August 2022, and March 2023 yielded 110 articles. The abstracts of these articles were examined to include those written since November 2011 and to exclude reviews and non-English articles. The panel reviewed 47 articles in full text, and 30 were found to fit the inclusion criteria. The panel methodologist assigned a level I rating to 19 studies and a level II rating to 11 studies. RESULTS: Data in the level I studies support the long-term effectiveness of SLT as primary treatment or as a supplemental therapy to glaucoma medications for patients with open-angle glaucoma. Several level I studies also found that SLT and argon laser trabeculoplasty (ALT) are equivalent in terms of safety and long-term efficacy. Level I evidence indicates that perioperative corticosteroid and nonsteroidal anti-inflammatory drug eye drops do not hinder the intraocular pressure (IOP)-lowering effect of SLT treatment. The impact of these eye drops on lowering IOP differed in various studies. No level I or II studies exist that determine the ideal power settings for SLT. CONCLUSIONS: Based on level I evidence, SLT is an effective long-term option for the treatment of open-angle glaucoma and is equivalent to ALT. It can be used as either a primary intervention, a replacement for medication, or an additional therapy with glaucoma medications. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

A Case of Uveitis-Glaucoma-Hyphema Syndrome Related to a Hydrus Microstent.

Uveitis-Glaucoma-Hyphema (UGH) syndrome is characterized by episodes of anterior chamber inflammation, elevated intraocular pressure and hyphema. It is caused by a mechanical chafing of the iris or ciliary body typically by a malpositioned intraocular lens. We present a rare case of UGH syndrome related to the insertion of a Hydrus Microstent. Because of the increased number of microinvasive glaucoma surgeries being performed and a reduction of UGH syndrome patients related to the insertion of intraocular lenses, it is an important diagnosis to consider in patients with recurrent postoperative inflammation.

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.

Non-invasive Measurement of the Viscoelasticity of the Optic Nerve and Sclera for Assessing Papilledema: A Pilot Clinical Study.

OBJECTIVE: The purpose of this study was to evaluate our novel ultrasound vibro-elastography (UVE) technique for assessing patients with papilledema by non-invasively measuring shear wave speed (SWS), elasticity and viscosity properties of the optic nerve and sclera. METHODS: Shear wave speeds were measured at three frequencies-100, 150 and 200 Hz-on the optic nerve and sclera tissues for assessing patients with papilledema resulting from idiopathic intracranial hypertension (IIH). The method was evaluated in six papilledema patients and six controls on two separate locations for each participant (i.e., optic nerve and posterior sclera). SWSs of the optic nerve and sclera were analyzed by using a 2-D speed map technique within a circular region of interest (ROI) (i.e., the diameter of the ROI was 1.5 mm × 3.0 mm at the optic nerve and sclera, respectively). Elasticity and viscosity were then analyzed using the wave speed dispersion over the three frequencies. RESULTS: We measured values of SWS at both locations, optic nerve and sclera, of the right eye and left eye at three different frequencies in IIH patients and controls. The SWS (mean ± standard deviation [m/s]) of the right eye was significantly higher at the sclera in IIH patients compared with controls (i.e., patients vs. controls: 5.91 ± 0.54 vs. 3.86 ± 0.56, p < 0.0001 at 100 Hz), but there was no significant difference at the optic nerve (i.e., patients vs. controls: 3.62 ± 0.39 vs. 3.36 ± 0.35, p = 0.1100 at 100Hz). We observed increased elasticity (kPa) in IIH patients, indicating there are significant differences in elasticity between patients and controls at the optic nerve and sclera (i.e., right eye [patients vs. controls]: 14.42 ± 6.59 vs. 6.5 ± 5.71, p = 0.0065 [optic nerve]; 33.04 ± 10.62 vs. 9.16 ± 7.15, p < 0.0001 [sclera]). Viscosity was also (Pa·s) higher in the sclera and optic nerve of the left eye (i.e., left eye [patient vs. control]: 8.89 ± 4.37 vs. 7.27 ± 5.01, p = 0.3790 (optic nerve); 16.05 ± 10.79 vs. 8.49 ± 6.09, p < 0.0194 [sclera]). CONCLUSION: This research illustrates the feasibility of using our UVE system to evaluate stiffness of different tissues in the eye non-invasively. It suggests that the viscoelasticity of the posterior sclera is higher than that of the optic nerve. We found that the posterior sclera is stiffer than the optic nerve in patients with papilledema resulting from IIH, making UVE a potential non-invasive technique for assessing papilledema.

Corneal Hysteresis for the Diagnosis of Glaucoma and Assessment of Progression Risk: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the current published literature on the utility of corneal hysteresis (CH) to assist the clinician in the diagnosis of glaucoma or in the assessment of risk for disease progression in existing glaucoma patients. METHODS: Searches of the peer-reviewed literature in the PubMed database were performed through July 2022. The abstracts of 423 identified articles were examined to exclude reviews and non-English articles. After inclusion and exclusion criteria were applied, 19 articles were selected, and the panel methodologist rated them for level of evidence. Eight articles were rated level I, and 5 articles were rated level II. The 6 articles rated level III were excluded. RESULTS: Corneal hysteresis is lower in patients with primary open-angle glaucoma, primary angle-closure glaucoma, pseudoexfoliative glaucoma, and pseudoexfoliation syndrome compared with normal subjects. Interpretation of low CH in patients with high intraocular pressure (IOP) or on topical hypotensive medications is complicated by the influence of these parameters on CH measurements. However, CH is also lower in treatment-naïve, normal-tension glaucoma patients compared with normal subjects who have a similar IOP. In addition, lower CH is associated with an increased risk of progression of glaucoma based on visual fields or structural markers in open-angle glaucoma patients, including those with apparently well-controlled IOP. CONCLUSIONS: Corneal hysteresis is lower in glaucoma patients compared with normal subjects, and lower CH is associated with an increased risk of disease progression. However, a causal relationship remains to be demonstrated. Nevertheless, measurement of CH complements current structural and functional assessments in determining disease risk in glaucoma suspects and patients. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Eye Dynamics and Engineering Network Consortium: Baseline Characteristics of a Randomized Trial in Healthy Adults.

PURPOSE: To improve understanding of intraocular pressure (IOP) and its variance, this project identifies systemic and ocular characteristics of healthy eyes of adult volunteers including IOP variation, ocular biometrics, and aqueous humor dynamics (AHDs). These data serve as baseline controls for further studies from the Eye Dynamics and Engineering Network (EDEN) Consortium. DESIGN: Multicenter open-label clinical trial in healthy adults randomized to 1 week treatment with 2 approved glaucoma drugs in a crossover design. PARTICIPANTS: Among 135 healthy participants, 122 participants (aged 55.2 ± 8.8 years; 92 females, 30 males) completed the protocol. METHODS: Participants from the University of Michigan, Mayo Clinic, and University of Nebraska Medical Center underwent measurements of ocular biometrics, AHD, and IOP using 4 tonometers. Intraocular pressure data during 3 study visits without glaucoma medications were used in the analysis. The PhenX Toolkit survey acquired standardized data on medical history, surgical history, medications, smoking and alcohol exposures, and physical measures. MAIN OUTCOME MEASURES: The variability of IOP measurements within eyes was assessed as visit-to-visit IOP variation, within-visit IOP variation, and within-visit positional IOP variation. The concordance (or correlation) between eyes was also assessed. RESULTS: Average positional change of > 4.7 mmHg was detected with a range of 0.5-11.0 mmHg. Pearson correlation of IOP between eyes within a visit was 0.87 (95% confidence interval [CI], 0.82-0.91) for Goldmann applanation tonometry, 0.91 (95% CI, 0.88-0.94) for Icare rebound tonometry, and 0.91 (95% CI, 0.88-0.94) for pneumatonometry. There was a 4% to 12% asymmetric fluctuation of 3 mmHg or more between eyes between visits using rebound tonometry, 9% with Goldmann applanation tonometry, and 3% to 4% by pneumotonometry. The coefficient of variation between visits for the same eye ranged from 11.2% to 12.9% for pneumatonometry, from 13.6% to 17.4% for rebound tonometry, and 15.8% to 16.2% for Goldmann applanation tonometry. CONCLUSIONS: The current study from the EDEN Consortium describes measurement methods and data analyses with emphasis on IOP variability. Future papers will focus on changes in ocular biometrics and AHD with timolol or latanoprost treatment. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Emerging drugs for the treatment of glaucoma: a review of phase II & III trials.

INTRODUCTION: Glaucoma is a progressive optic neuropathy and the leading cause of irreversible vision loss. By 2040, the number of individuals with glaucoma is expected to nearly double. The only known modifiable risk factor for glaucoma is intraocular pressure. Topical medications are often used as first-line therapies. Although there are numerous available treatments, there continues to be a need for the development of new medical therapies due to variable response, intolerable side-effect profiles in some patients, and elevated intraocular pressure refractory to other treatments. AREAS COVERED: This review will cover glaucoma medications currently undergoing phase II and III of drug development. EXPERT OPINION: There are numerous drugs currently in development that have demonstrated significant and clinically relevant reduction of intraocular pressure. Differentiating factors include improved tolerability, novel mechanisms of action, multiple mechanisms of action, or superior IOP reduction. However, the availability of generic prostaglandin analogs may limit adoption of these novel compounds as first-line agents, except for certain subgroups of glaucoma patients. Use as adjuvant or second-line therapy appears more likely for the majority of glaucoma patients.

Risk, Prevalence, and Progression of Glaucoma in Eyes With Age-Related Macular Degeneration Treated With Intravitreal Anti-Vascular Endothelial Growth Factor Injections.

PURPOSE: To examine the risk, prevalence, and progression of glaucoma development in age-related macular degeneration (AMD) eyes receiving intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections compared to controls. DESIGN: Retrospective clinical cohort study. METHODS: Retrospective review of eyes receiving intravitreal anti-VEGF injections from January 1, 2004, to December 31, 2013, for exudative AMD. Age- and sex-matched control groups of eyes included eyes with nonexudative AMD (NEAMD) and no AMD. Eyes with a diagnosis of glaucoma or glaucoma suspect were reviewed for injection details, type and date of glaucoma diagnosis, glaucoma treatments, standard automated perimetry (SAP), and spectral domain optical coherence tomography (SD-OCT). Qualitative progression was determined by indication of glaucoma progression in provider notes. Quantitative progression was assessed based on change in mean deviation (MD) on SAP, retinal nerve fiber layer thickness on SD-OCT, and intraocular pressure (IOP). RESULTS: There were 707 eyes of 504 patients treated with anti-VEGF injections and 1008 eyes in the NEAMD and no-AMD cohorts. There was no difference in glaucoma or suspect prevalence at initial presentation between eyes treated with injections and NEAMD (6.9% vs 9.7%, P = .22) or no-AMD controls (vs 8.5%, P = .55). There was no difference in cumulative 5-year probability of new glaucoma diagnosis after anti-VEGF injections compared to NEAMD (1.9% vs 1.0%, P = .69) or no-AMD controls (vs 1.6%, P = .88). There was no difference in qualitative progression of glaucoma in the injection cohort vs NEAMD (P = .19) or no-AMD controls (P = .61). The rate of MD change in injection eyes was similar to NEAMD eyes (P = .74) but greater than no-AMD eyes (P = .02). Eyes receiving injections required more topical glaucoma medications compared with NEAMD (P = .03) and more glaucoma laser treatments compared with no-AMD controls (P = .009). Eyes receiving injections did not require more frequent incisional glaucoma surgery compared with NEAMD (21.0% vs 15.0%, P = .95) or no-AMD controls (vs 10.0%, P = .10). CONCLUSION: Eyes treated with intravitreal anti-VEGF injections for exudative AMD did not have increased risk of developing glaucoma compared with controls. Of those with a glaucoma diagnosis, exudative AMD eyes receiving injections required a greater number of topical glaucoma medications compared with NEAMD eyes and had a greater rate of MD loss than no-AMD controls.

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.

Honeycomb Epithelial Edema Associated With Rho Kinase Inhibition: A Case Series and Review of the Literature.

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.

Effect of Topical Phenylephrine 2.5% on Episcleral Venous Pressure in Normal Human Eyes.

Purpose: Phenylephrine has been shown to affect intraocular pressure (IOP) but the mechanism of action is poorly understood. However, its action as a vasoconstrictor suggests possible effects on episcleral venous pressure (EVP). In this study, we evaluated the effect of phenylephrine on EVP and IOP in healthy subjects. Methods: Forty eyes of 20 subjects were included. Each subject received 3 drops of phenylephrine 2.5% in one eye at 1-minute intervals. The fellow eye served as control. Blood pressure, heart rate, and IOP and EVP of both eyes were measured at baseline, 15 minutes, and 60 minutes after instillation of phenylephrine. IOP was measured by pneumatonometry. EVP was assessed by using a computer-controlled episcleral venomanometer. Changes in IOP, EVP, blood pressure, and heart rate at 15 and 60 minutes were analyzed by paired t-tests. Results: IOP increased 15 minutes after instillation of phenylephrine in both treated (P = 0.001) and control eyes (P = 0.01) and returned to baseline at 60 minutes. The change in IOP at 15 minutes was not significantly different between the 2 groups. EVP in treated eyes was unchanged at 15 minutes (P = 0.8) but decreased significantly at 60 minutes (P < 0.001). In control eyes, there was no change in EVP at any time (P > 0.6). There were no significant changes from baseline in systolic and diastolic blood pressure and heart rate after instillation of phenylephrine. Conclusions: IOP elevation associated with topical phenylephrine is not caused by an increase in EVP in healthy subjects. Instead, EVP decreases with phenylephrine, but the mechanism remains to be determined.

The Effects of Topical Timolol and Latanoprost on Calculated Ocular Perfusion Pressure in Nonglaucomatous Volunteers.

Purpose: To characterize the effects of timolol and latanoprost on calculated ocular perfusion pressure (OPP) in a multicenter, prospective, crossover-design study. Methods: Nonglaucomatous volunteers were evaluated at baseline, after 1 week of timolol 0.5% dosed twice daily, and after 1 week of latanoprost 0.005% dosed nightly (randomized treatment order; 6-week washout period). Pneumatonometric intraocular pressure (IOP) and brachial blood pressure (BP) were evaluated at each visit. Using 3 commonly used equations, OPP was calculated based on IOP and BP. The OPPs at each visit were compared by using linear mixed-effects models. Results: This analysis includes 121 participants (242 eyes; 75% female, 87% White, mean age 55 years). Mean OPP (standard deviation) calculated with mean arterial pressure was 46.8 (8.1) mmHg at baseline, 48.5 (7.9) mmHg with timolol (P = 0.005), and 49.6 mmHg (8.2) with latanoprost (P < 0.001). When compared with baseline, OPP calculated with diastolic BP was significantly increased with both timolol (1.3 mmHg) and latanoprost (3.1 mmHg). The OPP calculated with systolic BP was increased with latanoprost (2.8 mmHg) but decreased with timolol (-1.3 mmHg). Timolol reduced systolic BP by 3.2 mmHg. Compared with timolol, latanoprost conferred greater increases in OPP calculated with both systolic and diastolic BP compared with baseline; however, the difference in treatment effects on OPP calculated with mean arterial pressure was not significantly different (P = 0.068). Conclusion: In this crossover study of nonglaucomatous volunteers, latanoprost increased OPP. However, timolol's benefit to OPP may be limited in part because it reduced systolic BP. Clinical Trial Registration number: NCT01677507.