Toric Monofocal Intraocular Lenses for the Correction of Astigmatism during Cataract Surgery: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the published literature evaluating the visual and refractive outcomes and rotational stability of eyes implanted with toric monofocal intraocular lenses (IOLs) for the correction of keratometric astigmatism during cataract surgery and to compare those outcomes with outcomes of eyes implanted with nontoric monofocal IOLs and other astigmatism management methods performed during cataract surgery. This assessment was restricted to the toric IOLs available in the United States. METHODS: A literature search of English-language publications in the PubMed database was last conducted in July 2022. The search identified 906 potentially relevant citations, and after review of the abstracts, 63 were selected for full-text review. Twenty-one studies ultimately were determined to be relevant to the assessment criteria and were selected for inclusion. The panel methodologist assigned each a level of evidence rating; 12 studies were rated level I and 9 studies were rated level II. RESULTS: Eyes implanted with toric IOLs showed excellent postoperative uncorrected distance visual acuity (UCDVA), reduction of postoperative refractive astigmatism, and good rotational stability. Uncorrected distance visual acuity was better and postoperative cylinder was lower with toric IOLs, regardless of manufacturer, when compared with nontoric monofocal IOLs. Correcting pre-existing astigmatism with toric IOLs was more effective and predictable than using corneal relaxing incisions (CRIs), especially in the presence of higher magnitudes of astigmatism. CONCLUSIONS: Toric monofocal IOLs are effective in neutralizing pre-existing corneal astigmatism at the time of cataract surgery and result in better UCDVA and significant reductions in postoperative refractive astigmatism compared with nontoric monofocal IOLs. Toric IOLs result in better astigmatic correction than CRIs, particularly at high magnitudes of astigmatism. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Central subfield thickness predicts visual acuity outcomes in plaque-irradiated eyes with choroidal melanoma.

OBJECTIVE: To determine the association between pre-operative central subfield thickness (CST) and post-radiotherapy visual acuity (VA), cystoid macular edema (CME), and intravitreal anti-vascular endothelial growth factor (VEGF) requirement. DESIGN: Single-center retrospective study. PARTICIPANTS: Patients with plaque-irradiated extramacular choroidal melanoma treated between 11/11/2011 and 4/30/2021. Pre-operative CST difference between the affected and unaffected eye was used. Kaplan-Meier analysis and hazard ratios were calculated. RESULTS: Of 85 patients, pre-operative CST was greater in the melanoma-affected eye (vs. fellow eye) by mean of 20.4 µm (median 14.0, range - 60.0-182.0). Greater CST at presentation (vs. fellow eye) was associated with larger tumor diameter (p = 0.02), greater tumor thickness (p < 0.001), and more frequent tumor-related Bruch's membrane rupture (p = 0.006). On univariate analysis of outcome data, greater CST at presentation (vs. fellow eye) was associated with higher 5-year risk (1.09 [1.02-1.17], p = 0.02) of VA 20/200 or worse and increased (1.10 [1.01-1.20], p = 0.03) likelihood for anti-VEGF injections after plaque irradiation. There was no significant association with CME. The association between CST and VA outcome remained significant on multivariate analysis accounting for impact of tumor thickness and radiation dose to optic disc, while tumor distance to fovea was the only significant factor on multivariate analysis for anti-VEGF injections. CONCLUSION: Greater CST at presentation (vs. fellow eye) was associated with worse VA outcome following plaque radiotherapy for choroidal melanoma. Large-sized tumors may contribute to a higher intraocular VEGF burden, potentially leading to greater preoperative CST, which correlates with poor VA outcome post-plaque radiotherapy.

Optical coherence tomography features in vitreoretinal lymphoma compared with non-infectious uveitis.

BACKGROUND: Vitreoretinal lymphoma (VRL) is a rare intraocular malignancy that poses a diagnostic challenge due to the non-specific clinical presentation that resembles uveitis. The use of spectral domain optical coherence tomography (SD-OCT) has emerged as a valuable imaging tool to characterize VRL. Therefore, we sought to determine the specific OCT features in VRL compared to the uveitides. METHODS: Retrospective chart review of patients who were seen at Mayo Clinic from January 1, 2010 through December 31, 2022. The medical records and SD-OCT images at time of initial presentation were reviewed in patients with biopsy-proven VRL, intermediate uveitis, or biopsy-confirmed sarcoid posterior uveitis. Patients with VRL or similar uveitides including intermediate uveitis or sarcoid posterior uveitis were included. RESULTS: There were 95 eyes of 56 patients in the VRL group and 86 eyes of 45 patients in the uveitis group, of whom 15 (33.3%) were diagnosed with intermediate uveitis and 30 (66.7%) with sarcoid chorioretinitis. The SD-OCT features more commonly seen at initial presentation in VRL patients (vs. uveitis) included preretinal deposits (31.6% vs. 9.3%, p = 0.002), intraretinal infiltrates (34% vs. 3.5%, p < 0.001), inner retinal hyperreflective spots (15.8% vs. 0%, p < 0.001), outer retinal atrophy (22.1% vs. 2.3%, p < 0.001), subretinal focal deposits (21.1% vs. 4.7%, p = 0.001), retinal pigmented epithelium (RPE) changes (49.5% vs. 3.5%, p < 0.001), and sub-RPE deposits (34.7% vs. 0%, p < 0.001). Features more frequently seen in uveitis included epiretinal membrane (ERM) (82.6% vs. 44.2%, p < 0.001), central macular thickening (95.3% vs. 51.6%, p < 0.001), cystoid macular edema (36% vs. 11.7%, p < 0.001), subretinal fluid (16.3% vs 6.4%, p = 0.04), and subfoveal fluid (16.3% vs. 3.2%, p = 0.003). Multivariate regression analysis controlling for age and sex showed absence of ERM (OR 0.14 [0.04,0.41], p < 0.001) and absence of central macular thickening (OR 0.03 [0,0.15], p = 0.02) were associated with VRL as opposed to uveitis. CONCLUSION: OCT features most predictive of VRL (vs. uveitis) included absence of ERM and central macular thickening.

American Academy of Ophthalmology Recommendations on Screening for Endogenous Candida Endophthalmitis.

The American Academy of Ophthalmology evaluated the practice of routine screening for intraocular infection from Candida septicemia. In the United States, ophthalmologists are consulted in the hospital to screen for intraocular infection routinely for patients with Candida bloodstream infections. This practice was established in the era before the use of systemic antifungal medication and the establishment of definitions of ocular disease with candidemia. A recent systematic review found a rate of less than 1% of routinely screened patients with endophthalmitis from Candida septicemia. Other studies found higher rates of endophthalmitis but had limitations in terms of inaccuracies in ocular disease classification, lack of vitreous biopsies, selection biases, and lack of longer-term visual outcomes. Some studies attributed ocular findings to Candida infections, rather than other comorbidities. Studies also have not demonstrated differences in medical management that are modified for eye disease treatment; therefore, therapy should be dictated by the underlying Candida infection, rather than be tailored on the basis of ocular findings. In summary, the Academy does not recommend a routine ophthalmologic consultation after laboratory findings of systemic Candida septicemia, which appears to be a low-value practice. An ophthalmologic consultation is a reasonable practice for a patient with signs or symptoms suggestive of ocular infection regardless of Candida septicemia.

Stroke Risk before and after Central Retinal Artery Occlusion: A Population-based Analysis.

PURPOSE: To determine the risk of stroke, transient ischemic attack (TIA), and transient monocular vision loss (TMVL) before and after a central retinal artery occlusion (CRAO). DESIGN: Population-based, retrospective case series. PARTICIPANTS: Patients diagnosed with a CRAO in Olmsted County, Minnesota, from 1976 to 2016. METHODS: Patients living in Olmsted County with a diagnosis code of CRAO from 1976 to 2016 were reviewed. New CRAOs were confirmed, and stroke, TIA, and TMVL events in the 15 days before and after CRAO were recorded. MAIN OUTCOME MEASURES: Incidence of stroke, TIA, and TMVL events in the 15 days before and after CRAO. RESULTS: Eighty-nine patients with a CRAO were identified, providing an annual incidence of 2.58/100 000 (95% confidence interval [CI], 2.04-3.11). Median age at the time of CRAO was 76 years (range, 46-100 years); 56.2% were male, and 89.9% of the cohort was White. In the 15 days before and after CRAO, there were 2 ischemic strokes (2.2%), 1 hemorrhagic stroke (1.1%), 2 TIAs (2.2%), and 9 TMVL events (10.1%). Starting in 1999, 15 of 45 patients underwent magnetic resonance imaging within 2 months of CRAO. One patient (6.7%) had evidence of asymptomatic diffusion restriction, and 9 patients (60%) had a remote infarct. CONCLUSIONS: This population-based study demonstrated that the risk of symptomatic ischemic stroke is 2.2% in the 15 days before and after a CRAO, which is slightly lower than most studies from tertiary centers. These data should be considered as practice recommendations are developed regarding the urgency of neurovascular workup in patients with acute CRAO.

OPTICAL COHERENCE TOMOGRAPHY FINDINGS IN CHOROIDAL MELANOMA-ASSOCIATED SUBRETINAL FLUID.

PURPOSE: To report optical coherence tomography findings of choroidal melanoma with subretinal fluid (SRF). METHODS: Single-center, retrospective review of spectral-domain optical coherence tomography in treatment-naive choroidal melanoma with associated SRF presenting between July 2009 and August 2021. RESULTS: Of 236 included patients, choroidal melanoma was small (n = 98, 41.5%), medium (n = 99, 41.9%), or large (n = 39, 16.5%). The most common optical coherence tomography feature was ellipsoid zone loss/disruption (n = 174, 73.7%), with unique features of bacillary layer detachment (n = 67, 28.4%), and heterogenous (n = 72, 30.5%) or homogenous (n = 48, 20.3%) subretinal hyperreflective material. Comparison (small vs. medium vs. large) revealed greater SRF extent with increasing tumor size (SRF ≥2 quadrants: 6.1% vs. 27.2% vs. 67.7%, P < 0.001). Ellipsoid zone disruption was less common in small tumors (52.0% vs. 86.9% vs. 94.9%, P < 0.001). Bacillary layer detachment was more common in medium tumors (16.3% vs. 40.4% vs. 28.2%, P < 0.001) and, compared with eyes without bacillary layer detachment, was associated with more SRF (minimal SRF vs. SRF ≥1 quadrant: likelihood ratio 18.8, P < 0.001) and more frequent heterogenous subretinal hyperreflective material (58.2% vs. 19.5%, P < 0.001). CONCLUSION: Optical coherence tomography features of choroidal melanoma-associated SRF vary by tumor size, with greater SRF extent in larger tumors, less ellipsoid zone disruption in small tumors, and more bacillary layer detachment in medium tumors.

EFFECT OF PHYSICIAN FACE MASK USE ON POSTINJECTION ENDOPHTHALMITIS.

PURPOSE: To examine the impact of physician face mask use on the rates and outcomes of postinjection endophthalmitis. METHODS: A multicenter retrospective, comparative cohort study comparing endophthalmitis rate and visual acuity of eyes that developed endophthalmitis after antivascular endothelial growth factor injections at Mayo Clinic Rochester (MCR) and at Mayo Clinic Health System sites depending on physician masking. RESULTS: A total of 164,824 injections were performed at MCR and Mayo Clinic Health System sites. Of these, 66,098 injections were in the no mask group and 98,726 injections were in the mask group. Overall, there were no differences in the rates of infectious endophthalmitis in the no mask versus mask cohorts (overall: no mask: 20 cases [0.0303%] vs. mask: 41 cases (0.0415%); P = 0.24; infectious: no mask: 12 cases [0.018%] versus mask: 13 cases [0.0132%]; P = 0.42). At MCR alone, there was a significant reduction in infectious endophthalmitis between the no mask versus mask groups (no mask: 9 cases [0.0297%] versus mask: 2 cases [0.003%]; P < 0.001). Only 2 cases of infectious endophthalmitis occurred at MCR after the face mask policy was implemented (1 in 30,000 injections). At presentation and at 6 months, the average visual acuity was similar for patients who developed endophthalmitis between the no mask versus mask groups. CONCLUSION: Physician face mask use did not affect the rate or outcome of postinjection endophthalmitis. However, there was a significant reduction at MCR after masking along with other quality improvement measures, including performance of injections in a dedicated procedure room and preparation of patients by nurses, that led to a low rate of endophthalmitis.

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.

Multifocal and Accommodating Intraocular Lenses for the Treatment of Presbyopia: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the published literature assessing the efficacy and safety of presbyopia-correcting intraocular lenses (IOLs) for the treatment of presbyopia after cataract removal. METHODS: Literature searches were undertaken in January 2018 and September 2020 in the PubMed, Medline, and Cochrane Library databases. This yielded 761 articles, of which 34 met the criteria for inclusion in this assessment and were assigned a level of evidence rating by the panel methodologist. Thirteen studies were rated level I and 21 studies were rated level II. RESULTS: Presbyopia-correcting lenses were effective at improving distance and near visual acuity after cataract surgery. Near acuity at different focal lengths was related directly to the effective add power of multifocal and extended depth-of-focus (EDOF) IOLs. Most multifocal and EDOF lenses that were compared with a control monofocal lens demonstrated that patient-reported spectacle independence was superior to the monofocal lens. All patients who had multifocal and EDOF lenses implanted showed decreased contrast sensitivity and reported more visual phenomena as compared with control participants who received monofocal lenses. CONCLUSIONS: Presbyopia-correcting lenses improve uncorrected near and distance visual acuity and decrease spectacle dependence after cataract surgery. Mesopic contrast sensitivity is decreased compared with monofocal lenses, and patient-reported visual phenomena are more likely in patients receiving multifocal or EDOF lenses.

Retinal Vein Occlusions Preferred Practice Pattern(®) Guidelines.

UNLABELLED: RETINAL VEIN OCCLUSIONS PREFERRED PRACTICE PATTERN® GUIDELINES: New evidence-based Retinal Vein Occlusions Preferred Practice Pattern® (PPP) guidelines, discussing the prognosis and risk factors of retinal vein occlusions and the treatment options.

Idiopathic Epiretinal Membrane and Vitreomacular Traction Preferred Practice Pattern(®) Guidelines.

UNLABELLED: IDIOPATHIC EPIRETINAL MEMBRANE AND VITREOMACULAR TRACTION PREFERRED PRACTICE PATTERN® GUIDELINES: New evidence-based Idiopathic Epiretinal Membrane and Vitreomacular Traction Preferred Practice Pattern® (PPP) guidelines, describing recommendations for the diagnosis, treatment, and management of patients.

Comprehensive Adult Medical Eye Evaluation Preferred Practice Pattern(®) Guidelines.

UNLABELLED: COMPREHENSIVE ADULT MEDICAL EYE EVALUATION® PREFERRED PRACTICE PATTERN® GUIDELINES: Evidence-based update of the Comprehensive Adult Medical Eye Evaluation Preferred Practice Pattern® (PPP) guidelines, discussing the rationale and components of an ophthalmic evaluation for adult patients with and without risk factors.

Comparison Among Methods of Retinopathy Assessment (CAMRA) Study: Smartphone, Nonmydriatic, and Mydriatic Photography.

PURPOSE: We compared smartphone fundus photography, nonmydriatic fundus photography, and 7-field mydriatic fundus photography for their abilities to detect and grade diabetic retinopathy (DR). DESIGN: This was a prospective, comparative study of 3 photography modalities. PARTICIPANTS: Diabetic patients (n = 300) were recruited at the ophthalmology clinic of a tertiary diabetes care center in Chennai, India. METHODS: Patients underwent photography by all 3 modalities, and photographs were evaluated by 2 retina specialists. MAIN OUTCOME MEASURES: The sensitivity and specificity in the detection of DR for both smartphone and nonmydriatic photography were determined by comparison with the standard method, 7-field mydriatic fundus photography. RESULTS: The sensitivity and specificity of smartphone fundus photography, compared with 7-field mydriatic fundus photography, for the detection of any DR were 50% (95% confidence interval [CI], 43-56) and 94% (95% CI, 92-97), respectively, and of nonmydriatic fundus photography were 81% (95% CI, 75-86) and 94% (95% CI, 92-96%), respectively. The sensitivity and specificity of smartphone fundus photography for the detection of vision-threatening DR were 59% (95% CI, 46-72) and 100% (95% CI, 99-100), respectively, and of nonmydriatic fundus photography were 54% (95% CI, 40-67) and 99% (95% CI, 98-100), respectively. CONCLUSIONS: Smartphone and nonmydriatic fundus photography are each able to detect DR and sight-threatening disease. However, the nonmydriatic camera is more sensitive at detecting DR than the smartphone. At this time, the benefits of the smartphone (connectivity, portability, and reduced cost) are not offset by the lack of sufficient sensitivity for detection of DR in most clinical circumstances.

Trends in Myopia and High Myopia from 1966 to 2019 in Olmsted County, Minnesota.

PURPOSE: To investigate the prevalence of myopia and high myopia in Olmsted County, Minnesota, from 1966 to 2019. DESIGN: Retrospective, cross-sectional, trend study. METHODS: Manifest refractions or lens prescription were converted to spherical equivalent (SE) to estimate the prevalence of adult myopia and high myopia. Age, sex, race, and visual acuity were recorded. Subjects with an SE of -0.5 diopters (D) or less were considered to have myopia; those with an SE of -6.0 D or less were considered to have high myopia. Exclusion criteria included visually significant cataract, pseudophakia, prior refractive surgery, or age less than 18 years. RESULTS: Among 81,706 sampled subjects, the myopia prevalence increased from 33.9% (95% CI, 31.1-36.8) in the 1960s to 57.1% (95% CI, 56.6-57.6) in the 2010s (P < .001). The high myopia prevalence increased from 2.8% (95% CI, 1.95-3.98) in the 1960s to 8.3% (95% CI, 8.08-8.62) in the 2010s (P < .001). Both male (32.0%-55.1%, P < .001) and female (40.6%-58.5%, P < .001) subjects experienced increasing myopia prevalence from the 1960s to the 2010s; both male (2.6%-7.4%, P < .001) and female (3.4%-9.1%, P < .001) subjects also had higher high myopia prevalence rates from the 1960s through the 2010s. Increasing myopia and high myopia prevalence was detected by decade in nearly all age groups (excluding 18- to 24-year-old high myopia subjects). White and Asian subjects had the highest myopia prevalence, whereas Black subjects had the lowest. From the 2000s to the 2010s, White (53.3%-57.0%, P < .001) and Black (41.0%-47.0%, P = .001) subjects had significant increases in myopia prevalence. The mean SE decreased from the 1960s (-0.42 D; 95% CI, -0.59 to +2.49) to the 2010s (-1.85 D; 95% CI, -1.88 to +2.96) (P < .001). CONCLUSIONS: From 1966 to 2019 in Olmsted County, Minnesota, there was a 68% and 199% increase in myopia and high myopia prevalence, respectively.

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.

Subretinal drusenoid deposits, age-related macular degeneration, and cardiovascular disease.

Decades of studies on age-related macular degeneration (AMD), cardiovascular disease and stroke have not found consistent associations between AMD and systemic vascular disease. This study suggests that there is in fact no general relationship, but instead a strong, specific association between only the subretinal drusenoid deposit (SDD) phenotype of AMD on retinal imaging and certain co-existent vascular diseases that are high risk for compromised cardiac output or internal carotid artery stenosis. Future screening initiatives for these high -risk vascular diseases (HRVDs) with fast, inexpensive retinal imaging could make a significant contribution to public health and save lives. Likewise, screening patients with known HRVDs for unrecognized AMD of the SDD form could enable needed treatment and save vision.

A Comparative Study of Responses to Retina Questions from Either Experts, Expert-Edited Large Language Models, or Expert-Edited Large Language Models Alone.

Objective: To assess the quality, empathy, and safety of expert edited large language model (LLM), human expert created, and LLM responses to common retina patient questions. Design: Randomized, masked multicenter study. Participants: Twenty-one common retina patient questions were randomly assigned among 13 retina specialists. Methods: Each expert created a response (Expert) and then edited a LLM (ChatGPT-4)-generated response to that question (Expert + artificial intelligence [AI]), timing themselves for both tasks. Five LLMs (ChatGPT-3.5, ChatGPT-4, Claude 2, Bing, and Bard) also generated responses to each question. The original question along with anonymized and randomized Expert + AI, Expert, and LLM responses were evaluated by the other experts who did not write an expert response to the question. Evaluators judged quality and empathy (very poor, poor, acceptable, good, or very good) along with safety metrics (incorrect information, likelihood to cause harm, extent of harm, and missing content). Main Outcome: Mean quality and empathy score, proportion of responses with incorrect information, likelihood to cause harm, extent of harm, and missing content for each response type. Results: There were 4008 total grades collected (2608 for quality and empathy; 1400 for safety metrics), with significant differences in both quality and empathy (P < 0.001, P < 0.001) between LLM, Expert and Expert + AI groups. For quality, Expert + AI (3.86 ± 0.85) performed the best overall while GPT-3.5 (3.75 ± 0.79) was the top performing LLM. For empathy, GPT-3.5 (3.75 ± 0.69) had the highest mean score followed by Expert + AI (3.73 ± 0.63). By mean score, Expert placed 4 out of 7 for quality and 6 out of 7 for empathy. For both quality (P < 0.001) and empathy (P < 0.001), expert-edited LLM responses performed better than expert-created responses. There were time savings for an expert-edited LLM response versus expert-created response (P = 0.02). ChatGPT-4 performed similar to Expert for inappropriate content (P = 0.35), missing content (P = 0.001), extent of possible harm (P = 0.356), and likelihood of possible harm (P = 0.129). Conclusions: In this randomized, masked, multicenter study, LLM responses were comparable with experts in terms of quality, empathy, and safety metrics, warranting further exploration of their potential benefits in clinical settings. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of the article.