Bilateral optic neuropathy associated with lorlatinib monotherapy for ALK-positive metastatic lung adenocarcinoma.

Purpose: This report details the characteristics of a case of bilateral optic neuropathy during treatment with oral lorlatinib for ALK-positive metastatic adenocarcinoma of the lung. Observations: A 57-year-old woman with metastatic adenocarcinoma of the lung receiving treatment with lorlatinib presented to the ophthalmology urgent care with bilateral loss of vision that had progressed to no light perception over the previous 2 weeks. She was hospitalized for an extensive autoimmune, infectious, neoplastic, and paraneoplastic workup, which revealed enhancement of both optic nerves extending up to the optic chiasm and an area of restricted diffusion in the splenium of the corpus callosum on MRI. Lorlatinib was discontinued by her oncologist and she received treatment with five days of pulse-dose intravenous solumedrol as well as five days of plasmapheresis with gradual improvement in her vision. In follow-up, her vision had improved to 20/40 and 20/30. Conclusion and importance: There have been few reports describing vision loss associated with lorlatinib, an ALK/ROS1 targeted tyrosine kinase inhibitor used to treat metastatic lung adenocarcinoma. This report details the characteristics of a case of bilateral retrobulbar optic neuropathy as well as the treatment and recovery of such a case. Further exploration is needed in order to improve our understanding of the pathogenesis of this rare but potentially devastating adverse effect.

Assessment of Remote Training, At-Home Testing, and Test-Retest Variability of a Novel Test for Clustered Virtual Reality Perimetry.

OBJECTIVE: To assess the feasibility of remotely training glaucoma patients to take a 10-session clustered virtual reality (VR) visual field (VF) test (Vivid Vision Perimetry [VVP-10]) at home, analyze results for test-retest variability, and assess correspondence with conventional perimetry. DESIGN: Cross-sectional study. SUBJECTS: Twenty-one subjects with glaucoma were enrolled and included in the feasibility assessment of remote training. Thirty-six eyes were used for test-retest analysis and determination of concordance with the Humphrey Field Analyzer (HFA). METHODS: Subjects were provided with a mobile VR headset containing the VVP-10 test software and trained remotely via video conferencing. Subjects were instructed to complete 10 sessions over a 14-day period. MAIN OUTCOME MEASURES: Feasibility was determined by the number of subjects who were able to independently complete VVP-10 over the 14-day period after 1 remote training session. The intraclass correlation coefficient (ICC) for average fraction seen across 10 sessions and the standard error (SE) of the mean were primary outcome measures for assessing test-retest variability. Correlation with HFA mean sensitivity (MS) across eyes, was a secondary outcome measure. RESULTS: Twenty subjects (95%) successfully completed the VVP-10 test series after 1 training session. The ICC for VVP-10 was 0.95 (95% confidence interval [CI], 0.92-0.97). The mean SE in units of fraction seen was 0.012. The Spearman correlations between VVP-10 average fraction seen and HFA MS were 0.87 (95% CI, 0.66-0.98) for moderate-to-advanced glaucoma eyes, and decreased to 0.67 (95% CI, 0.28-0.94) when all eyes were included. CONCLUSIONS: Remote training of patients at home is feasible, and subsequent remote clustered VF testing using VVP-10 by patients on their own, without any further interactions with caregivers or study staff, was possible. At-home VVP-10 results demonstrated low test-retest variability. Future studies must be conducted to determine if VVP-10, taken at home as convenient for the patient, may be a viable supplement to provide equivalent or complementary results to that of standard in-clinic assessment of visual function in glaucoma. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Pathogen Surveillance for Acute Infectious Conjunctivitis.

Importance: Acute infectious conjunctivitis is a common ocular condition with major public health consequences. Objective: To assess regional variations and microbial etiologies of acute infectious conjunctivitis to guide treatment. Design, Setting, and Participants: In this cross-sectional study, patients with presumed acute infectious conjunctivitis were enrolled in the study at 5 sites (Honolulu, Hawaii; Los Angeles, San Francisco, and San Diego, California; and Petah-Tikva, Israel) from March 2021 to March 2023. Patients with allergic or toxic conjunctivitis were excluded. Main Outcomes and Measures: Pathogens were identified by unbiased RNA deep sequencing. Results: In all, 52 patients (mean [range] age, 48 [7-80] years; 31 females [60%]) were enrolled at 5 sites (6 patients from Honolulu, 9 from San Diego, 11 from Los Angeles, 13 from San Francisco, and 13 from Petah-Tikva). RNA deep sequencing detected human adenovirus species D in one-quarter of patients (13 of 52). A wide range of pathogens, including human coronavirus 229E, SARS-CoV-2, and herpes simplex virus type 1, was also identified, as well as several bacteria and fungi. Moreover, 62% (32 of 52) of patients presented with purulent discharge, while only 8% (4 of 52) of patients had confirmed bacterial pathogens. Conclusion and Relevance: In this cross-sectional study, pathogens associated with acute infectious conjunctivitis varied between all 5 sites in the US and Israel. Purulent discharge was a common presenting sign in this study, with a low specificity for bacteria-associated conjunctivitis, suggesting that further diagnostic workup may be necessary to inform antibiotic stewardship. Additional research on cost-effectiveness of using RNA deep sequencing is needed to ascertain whether it is better to monitor patients clinically until resolution of disease.

Socioeconomic Correlates of Keratoconus Severity and Progression.

PURPOSE: The purpose of this study was to investigate the social determinants of health for keratoconus. METHODS: In this retrospective cohort study of patients with keratoconus, the electronic health record was reviewed for keratometry, treatments received, clinical comorbidities, and social characteristics. Outcomes included severe keratoconus at presentation (steep keratometry ≥52 diopters), disease progression (≥0.75 diopters increase from the first to the most recent clinical visit), and corneal transplantation. Logistic regression was used to evaluate factors associated with severity at presentation and corneal transplantation. Cox proportional hazards modeling was used to evaluate progression. RESULTS: A total of 1038 patients with keratoconus were identified, 725 (70%) of whom had baseline imaging. Compared with commercially insured patients, Medicaid recipients were more likely to have severe keratoconus, independent of social and clinical confounders [odds ratio (OR) 1.94, 95% confidence interval (CI), 1.12-3.35, P = 0.017]. Male sex was independently associated with progression (hazard ratio = 1.38, 95% CI, 1.03-1.84, P = 0.030). Medicare and Medicaid recipients were more likely to require transplantation compared with commercially insured patients (OR 2.71, 95% CI, 1.65-4.46, P < 0.001 and OR 1.74, 95% CI, 1.08-2.80, P = 0.022, respectively). Other social determinants of health, including non-White race/ethnicity, limited English proficiency, and unemployment, were associated with the outcomes only in univariate analysis. Obstructive sleep apnea, atopy, body mass index, and tobacco use were not associated with any outcome. CONCLUSIONS: Socioeconomic factors were more consistent predictors of keratoconus severity and corneal transplantation compared with clinical factors that have received relatively greater attention in the keratoconus literature.

Parental Keratoconus Literacy: A Socioeconomic Perspective.

Purpose: To assess the impact of parental socioeconomic status and keratoconus literacy on pediatric eye rubbing and keratoconus severity. Methods: In this mixed-methods study, pediatric keratoconus patients (age ≤ 18 years) were retrospectively identified. Sociodemographic and clinical characteristics were extracted from the electronic medical record (EMR). Telephone surveys were subsequently conducted to assess parental keratoconus literacy, receipt of counseling on keratoconus prevention, eye rubbing, and household socioeconomic factors not available in the EMR. Parents reporting poor keratoconus literacy were probed via semi-structured interview to explore barriers to their understanding. Results: Forty-eight patients met inclusion criteria, 22 (46%) of whom were reached by telephone. Most patients were insured by Medicaid (73%) and current eye rubbers (82%). Few parents reported good or excellent keratoconus literacy now (32%) or at the time of diagnosis (18%). Parents with a high-school education, limited English proficiency, lower income level, and Medicaid insurance tended to have lower keratoconus literacy, though this was not statistically significant. Parental keratoconus literacy was not correlated with disease severity. High-school education, limited English proficiency, lower income level, and Medicaid insurance were correlated with steeper keratometry readings, which was statistically significant for high-school education. In-depth interviews revealed parents felt unconfident with eye health in general and perceived a personal responsibility for learning more. Conclusion: This is the first study exploring keratoconus literacy from a socioeconomic perspective, demonstrating lower literacy among socioeconomically marginalized parents and a tendency toward more severe disease in their children.

Trends in Corneal Topography and Tomography Imaging for Keratoconus Management.

Purpose: To describe trends in the use of corneal topography and tomography for the management of keratoconus patients at a single academic institution and to identify how these trends may be associated with different procedural interventions. Patients and Methods: In this retrospective cohort study, keratoconus patients treated from 2012 to 2019 were identified. The electronic health record was reviewed for the presence of corneal topography or tomography imaging completed within seven days of the first visit and the highest level of intervention at the first and most recent visit. Patients were grouped as pediatric (<18 years) or adult (≥18 years). Chi-square tests and linear regressions were used to evaluate trends and to determine which factors were predictive for receiving corneal collagen cross-linking (CXL) versus other surgical interventions (intrastromal corneal ring segments, lamellar keratoplasty, or penetrating keratoplasty) by the most recent visit. Results: A total of 873 keratoconus patients met inclusion criteria. The use of corneal topography at the first visit remained relatively consistent from 2012 to 2019, while corneal tomography usage at the first visit increased from 3.9% in 2015, when corneal tomography was introduced, to 52.8% in 2019. Each year was associated with an 11.2% ± 1.9% increase in the use of corneal tomography at the first visit in pediatric patients and 6.7% ± 0.5% in adult patients. Use of corneal tomography at the first visit was a significant predictor for receiving CXL procedures (P < 0.001) and a negative predictor for requiring other surgical interventions (P = 0.032) when controlling for the year of the first visit. Conclusion: Obtaining corneal tomography at the first visit has become the standard of care in keratoconus, especially for pediatric patients. Moreover, the increase in corneal tomography imaging has coincided with an increase in CXL procedures and decrease in other surgical interventions.

A Global and Sector-Based Comparison of OCT Angiography and Visual Field Defects in Glaucoma.

Purpose: To evaluate the correlation of optical coherence tomography angiography (OCTA) and spectral-domain optical coherence tomography (SD-OCT) with visual field for global and sector-based indices among glaucoma and glaucoma-suspected eyes. Patients and Methods. This is a retrospective study, and in total, 48 glaucoma eyes and 31 glaucoma suspect eyes were included. The correlation between visual field parameters and radial peripapillary capillary (RPC) vessel density via OCTA was compared to the correlation with retinal nerve fiber layer (RNFL) thickness via SD-OCT. The RPC vessel density and RNFL thickness were divided into eight sectors, which included the temporal upper, temporal lower, superotemporal, inferotemporal, superonasal, inferonasal, nasal upper, and nasal lower sectors. Pearson correlations with 95% confidence intervals were calculated with resampling, and correlations were compared with a Fisher Z transformation. Results: Both RPC vessel density (R = 0.63, 95% CI [0.24, 0.86]) and RNFL thickness (R = 0.49, 95% CI [0.23, 0.69]) were correlated with the mean deviation when comparing global indices of glaucoma patients. In glaucoma suspects, the correlations between the mean deviation and RPC vessel density (R = 0.21, 95% CI [-0.05, 0.49]) and RNFL thickness (R = 0.01, 95% CI [-0.35, 0.39]) were not significant. Glaucoma eyes had the highest correlation between the mean sensitivity and RPC vessel density and RNFL thickness for the superotemporal, superonasal, temporal upper, and inferotemporal sectors. Conclusion: Across a diverse population and heterogeneous glaucoma types, RPC vessel density measurements correlate with global and sector-wise visual field indices similar to RNFL thickness.

Efficacy of Care and Antibiotic Use for Chalazia and Hordeola.

OBJECTIVES: To evaluate whether use of an antibiotic improves the efficacy of care for a chalazion or hordeolum. METHODS: A cross-sectional retrospective review was performed. All patients treated for a newly diagnosed chalazion or hordeolum at the University of California, San Francisco from 2012 to 2018 were identified. Patients were excluded when clinical notes were inaccessible or there was inadequate documentation of treatment modality or outcome. Patient demographics, setting of initial presentation, treatment modalities, antibiotic use, and outcomes were analyzed. RESULTS: A total of 2,712 patients met inclusion criteria. Management with an antibiotic was observed in 36.5% of patients. An antibiotic was 1.53 times (95% confidence interval [CI], 1.06-2.22, P=0.025) more likely to be prescribed in emergency or acute care setting for a chalazion. Older age was associated with a higher risk of receiving an antibiotic for a hordeolum (adjusted RR 1.07 per decade, 95% CI, 1.05-1.11, P<0.001). The addition of an antibiotic to conservative measures for a chalazion (adjusted RR, 0.97, 95% CI, 0.89-1.04, P=0.393) or hordeolum (adjusted RR, 0.99, 95% CI, 0.96-1.02, P=0.489) was not associated with an increased likelihood of treatment success. CONCLUSION: Although frequently prescribed, an antibiotic is unlikely to improve the resolution of a chalazion or hordeolum.

Asymmetric Functional Impairment of ON and OFF Retinal Pathways in Glaucoma.

Purpose: To investigate ON-pathway versus OFF-pathway dysfunction in glaucoma using handheld electroretinography (ERG) with a temporally modulated sinusoidal flicker stimulus. Design: Cross-sectional study. Participants: Fifty-nine participants accounting for 104 eyes, comprised of 19 control eyes, 26 glaucoma suspect eyes, and 59 glaucoma eyes. Methods: Participants underwent portable ERG testing, which included the photopic flash, photopic flicker, photopic negative response stimulus, ON-OFF stimulus, and a custom-written sinusoidal flicker stimulus that was modulated from 50 to 0.3 Hz. Main Outcome and Measures: The ERG response amplitudes were measured by the handheld ERG. For the custom-written sinusoidal flicker stimulus, we derived and compared the log10 first harmonic frequency response amplitudes. Patient discomfort and fatigue after ERG testing were rated on a scale from 1 to 5. Results: Baseline demographics were not significantly different between groups, except for ocular characteristics. Analysis was performed adjusting for participant age, sex, race, and dilation status, and the sinusoidal frequency responses were stratified at 10 Hz because higher frequencies are associated with the OFF-pathway, whereas lower frequencies are associated with the ON-pathway. After stratification, glaucoma eyes showed an adjusted decrease of 32.1% at frequencies of more than 10 Hz (95% confidence interval [CI], -51.8% to -4.1%; P = 0.03). For 10 Hz stimulus frequencies or less, an adjusted 11.5% reduction was found (95% CI, -39.5% to 29.1%; P = 0.50). Glaucoma suspect eyes did show a decreased response, but this was not significant at either frequency range. When comparing handheld ERG with traditional visual field assessments, participants found the handheld ERG to result in much less discomfort and fatigue. Conclusions: Our finding that glaucoma participants showed greater decreases in ERG response at higher frequencies supports the hypothesis that the OFF-pathway may be more vulnerable in human glaucoma. Using a handheld ERG device with a sinusoidal flicker stimulus may provide an objective assessment of visual function in glaucoma.

Single Ophthalmology Program Trends in Resident Surgical and Research Productivity by Gender, Underrepresented Minority Status, and Welcoming a Child.

Objective The aim of the study is to identify differences for cataract surgery, total procedural volume, and publication rates between residents by gender, underrepresented minority (URM) status, and welcoming a child during ophthalmology residency. Design This is a retrospective, cross-sectional study. Participants A total of 89 residents graduating from 2002 to 2020 at a single program were included. Methods A multiple linear regression model was created to determine factors predictive of the number of cataract surgeries performed as the primary surgeon, total procedural volume, number of publications, or first author publications. Independent variables included resident gender, URM status, PhD degree, welcoming a child during residency, and graduation year. Results Of the 89 graduating residents included in this study, identifying as female (45 women, 50.6%) and as URM (eight identifying as URM, 9.0%) was not associated with a difference in surgical or research volume. Female residents performed a mean (SD) of 240.1 (55.1) cataract surgeries while male residents performed 210.6 (46.1) cataract surgeries. Residents identifying as URM completed 228.1 (41.9), while non-URM residents completed 234.8 (51.9) cataract surgeries. Since 2008, eight female residents (22.2%) and two male residents (6.9%) added children to their families. Welcoming a child to the family was also not associated with decreased surgical or publication volume. Number of cataract surgeries, total procedures, and number of publications did increase over time ( p <0.001), as each graduation year was associated with 5.4 (95% CI: 3.9, 7.1) more cataract surgeries and 30.5 (95% CI: 25.7, 36.9) more procedures. Each year was also associated with 0.24 (95% CI: 0.09, 0.38) more publications and 0.18 (95% CI: 0.08, 0.28) more first author publications. Conclusion Surgical and research productivity has increased, and female residents and residents who identify as URM did not have fewer cataract surgeries or procedures. Welcoming a child also did not correlate with differences in surgical or procedural volume. Programs should continue to promote equitable surgery and procedural distributions as well as identify more targeted strategies to encourage and recruit underrepresented medical students into ophthalmology.

Probing ON and OFF Retinal Pathways in Glaucoma Using Electroretinography.

Glaucoma is a progressive neurodegenerative disease involving damage and eventually death of retinal ganglion cells (RGCs) that comprise the optic nerve. This review summarizes current understanding of specific RGC type vulnerability in glaucoma and how electroretinography (ERG) may provide an objective measure of these functional perturbations. There is building evidence to suggest that ON RGCs, which respond to light increments, may be more resilient to elevated intraocular pressure and glaucoma, whereas OFF RGCs, which respond to light decrements, may be more susceptible. ERG experiments in nonhuman primates and mice have also shown that the ON- and OFF-pathways can be separated using a variety of techniques such as pattern ERG and the photopic negative response. Another ERG paradigm of interest to separate the ON and OFF responses is a flicker stimulus at varying temporal frequencies. Response to lower temporal frequencies is associated with the ON-pathway, and ERG response to higher frequencies is associated with the OFF-pathway. In mice, experimental glaucoma models have shown greater decreases in ERG response at higher frequencies, suggesting that the OFF-pathway is more susceptible. We also summarize current clinical ERG protocols used for glaucoma and discuss innovations for developing new types of stimuli that can further separate the ON- and OFF-pathways. Applying these novel paradigms that distinguish ON- and OFF-pathways may ultimately improve glaucoma diagnostics and monitoring of glaucoma progression. Translational Relevance: Based on our current understanding of specific RGC type vulnerability in glaucoma, we explore how ERG may provide an objective measure of ON- versus OFF-pathway functional perturbations.