Sit, Arthur J.

Précis: In our study of the factors predictive of latanoprost response, we found that normotensive subjects with higher intraocular pressure, lower uveoscleral outflow, and higher body mass index had a greater response to 1-week treatment. Purpose: To evaluate relationships between variable intraocular pressure (IOP) responses to latanoprost and participant characteristics, baseline values and changes in aqueous humor dynamics (AHD) parameters. Methods: We assessed 226 eyes from 113 healthy participants. AHD parameters measured at baseline and after 1-week treatment with latanoprost included: IOP by pneumatonometry, episcleral venous pressure (EVP) by venomanometry, aqueous humor flow rate by fluorophotometry, outflow facility by 2-minute pneumatonography, and uveoscleral outflow calculated using the modified Goldmann equation. IOP responses were categorized into 4 groups: nonresponders (<10% reduction), all-responders (≥10% reduction), medium-responders (10%–20% reduction), and high-responders (≥20% reduction). Generalized estimating equation models were used to analyze treatment effects and compare groups. Results: Baseline IOP was higher in high-responders than medium-responders and nonresponders ( P =0.007 and P <0.001, respectively). Body mass index (BMI) was significantly higher in high-responders and all-responders compared with nonresponders ( P =0.02 and P =0.03, respectively). Responders had lower baseline uveoscleral outflow ( P =0.03). There were no significant differences in other baseline characteristics including EVP, outflow facility, and aqueous flow rate between the 4 groups. IOP decreased while outflow facility and uveoscleral outflow increased after latanoprost treatment in all responder groups but did not change in nonresponders. EVP and aqueous flow rate did not change significantly in any group. The change in uveoscleral outflow was greater in high-responders than in nonresponders ( P =0.004). Conclusions: In healthy subjects, higher baseline IOP, lower uveoscleral outflow and higher BMI are predictors of a greater IOP reduction by latanoprost. A greater increase in uveoscleral outflow is responsible for this larger response.

Purpose: To identify reasons for variable intraocular pressure (IOP) responses to latanoprost and timolol in healthy volunteers and to generate the control group as part of Eye Dynamics and Engineering Network. Methods: In this multicenter, randomized, crossover study (NCT01677507), both eyes of 106 healthy subjects (212 eyes) were treated with latanoprost or timolol for 7 days, with a 6-week washout between treatments. Ocular biometrics, tonometry, and aqueous humor dynamics (AHD) were assessed at baseline and day 8 of each treatment. Subjects were divided into responders and nonresponders using cutoffs of >15% or >10% IOP reduction. Treatment effects and correlations were analyzed with paired t-tests. Results: More subjects responded to latanoprost (54%) than timolol (27%) at >15% cutoff ( p < 0.01). Responders had higher mean baseline IOP than nonresponders for both drugs at both cutoffs ( p < 0.01). Among timolol nonresponders ( n = 56), 39% responded to latanoprost in both eyes, 20% in one eye, and 41% in neither. Among latanoprost nonresponders ( n = 31), 13% responded to timolol in both eyes, 13% in one eye, and 74% in neither. Latanoprost increased uveoscleral outflow, while timolol reduced aqueous flow and outflow facility. Low baseline uveoscleral outflow was associated with latanoprost response. Conclusions: Higher baseline IOP predicted better responses to both drugs. Higher baseline uveoscleral outflow predicted nonresponse to latanoprost. No AHD differences were linked to the timolol response. Timolol nonresponders were often responsive to latanoprost, but not vice versa.

ImportanceSpecialized ophthalmology terminology limits comprehension for nonophthalmology clinicians and professionals, hindering interdisciplinary communication and patient care. The clinical implementation of large language models (LLMs) into practice has to date been relatively unexplored.ObjectiveTo evaluate LLM–generated plain language summaries (PLSs) integrated into standard ophthalmology notes (SONs) in improving diagnostic understanding, satisfaction, and clarity.Design, Setting, and ParticipantsRandomized quality improvement study conducted from February 1, 2024, to May 31, 2024, including data from inpatient and outpatient encounters in a single tertiary academic center. Participants were nonophthalmology clinicians and professionals and ophthalmologists. The single inclusion criterion was any encounter note generated by an ophthalmologist during the study dates. Exclusion criteria were (1) lack of established nonophthalmology clinicians and professionals for outpatient encounters and (2) procedure-only patient encounters.InterventionAddition of LLM-generated plain language summaries to ophthalmology notes.Main Outcomes and MeasuresThe primary outcome was survey responses from nonophthalmology clinicians and professionals assessing understanding, satisfaction, and clarity of ophthalmology notes. Secondary outcomes were survey responses from ophthalmologists evaluating PLS in terms of clinical workflow and accuracy, objective measures of semantic quality, and safety analysis.ResultsA total of 362 (85%) nonophthalmology clinicians and professionals (33.0% response rate) preferred the PLS to SON. Demographic data on age, race and ethnicity, and sex were not collected. Nonophthalmology clinicians and professionals reported enhanced diagnostic understanding (percentage point increase, 9.0; 95% CI, 0.3-18.2; P = .01), increased note detail satisfaction (percentage point increase, 21.5; 95% CI, 11.4-31.5; P &amp;lt; .001), and improved explanation clarity (percentage point increase, 23.0; 95% CI, 12.0-33.1; P &amp;lt; .001) for notes containing a PLS. The addition of a PLS was associated with reduced comprehension gaps between clinicians who were comfortable and uncomfortable with ophthalmology terminology (from 26.1% [95% CI, 13.7%-38.6%; P &amp;lt; .001] to 14.4% [95% CI, 4.3%-24.6%; P &amp;gt; .06]). PLS semantic analysis found high meaning preservation (bidirectional encoder representations from transformers score mean F1 score: 0.85) with greater readability than SONs (Flesch Reading Ease: 51.8 vs 43.6; Flesch-Kincaid Grade Level: 10.7 vs 11.9). Ophthalmologists (n = 489; 84% response rate) reported high PLS accuracy (90% [320 of 355] a great deal) with minimal review time burden (94.9% [464 of 489] ≤1 minute). PLS error rate on ophthalmologist review was 26% (126 of 489). A total of 83.9% (104 of 126) of errors were deemed low risk for harm and none had a risk of severe harm or death.Conclusions and RelevanceIn this study, use of LLM-generated PLSs was associated with enhanced comprehension and satisfaction among nonophthalmology clinicians and professionals, which might aid interdisciplinary communication. Careful implementation and safety monitoring are recommended for clinical integration given the persistence of errors despite physician review.

Purpose: Evaluate the relationship between CYP3A4 phenotype, the gene encoding the enzyme that metabolizes exogenous steroids, and the rate of steroid-induced intraocular pressure (IOP) response. Materials and Methods: Lymphocyte-derived DNA sequencing of CYP3A4 from 10073 patients was completed using the PGRN-Seq assay. Subjects with CYP3A4 intermediate metabolizer or slower phenotypes were identified and compared with controls matched by age, race, and sex. All subjects had at least 3 eye exams with at least an exam while on topical/systemic/local steroid in any body location except the eye. Patients with pre-existing glaucoma or glaucoma suspects were excluded. Results: Of the 10,073 patients, there were 63 patients who had CYP3A4 poor or intermediate metabolizer phenotype. Of the 63 patients, 22 had documented steroid use. Fifty-nine percent (13/22) of patients with CYP3A4 poor/intermediate metabolizer had a steroid-induced IOP response of 3 mm Hg or more, significantly higher compared with 23% (5/22) of matched controls (P=0.031). Although more poor/intermediate metabolizers were steroid responders, the average IOP elevation in steroid responders in both groups was similar (5.0±2.5 mm Hg in CYP3A4 poor/intermediate metabolizers compared with 4.1±2.1 mm Hg in controls, P=0.327). Family history of glaucoma was similar in both groups (7/22 vs. 8/22, P=1.0). Conclusion: Reduced CYP3A4 phenotypes may help identify patients at a higher risk of steroid-induced IOP elevation.

Précis: 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.