Features Associated with Visible Lamina Cribrosa Pores in Individuals of African Ancestry with Glaucoma: Primary Open-Angle African Ancestry Glaucoma Genetics (POAAGG) Study.

There are scarce data regarding the rate of the occurrence of primary open-angle glaucoma (POAG) and visible lamina cribrosa pores (LCPs) in the eyes of individuals with African ancestry; the potential impact of these features on disease burden remains unknown. We recruited subjects with POAG to the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study. Through regression models, we evaluated the association between the presence of LCPs and various phenotypic features. In a multivariable analysis of 1187 glaucomatous eyes, LCPs were found to be more likely to be present in eyes with cup-to-disc ratios (CDR) of ≥0.9 (adjusted risk ratio (aRR) 1.11, 95%CI: 1.04-1.19, p = 0.005), eyes with cylindrical-shaped (aRR 1.22, 95%CI: 1.11-1.33) and bean pot (aRR 1.24, 95%CI: 1.13-1.36) cups versus conical cups (p < 0.0001), moderate cup depth (aRR 1.24, 95%CI: 1.06-1.46) and deep cups (aRR 1.27, 95%CI: 1.07-1.50) compared to shallow cups (p = 0.01), and the nasalization of central retinal vessels (aRR 1.33, 95%CI: 1.23-1.44), p < 0.0001). Eyes with LCPs were more likely to have a higher degree of African ancestry (q0), determined by means of SNP analysis (aRR 0.96, 95%CI: 0.93-0.99, p = 0.005 for per 0.1 increase in q0). Our large cohort of POAG cases of people with African ancestry showed that LCPs may be an important risk factor in identifying severe disease, potentially warranting closer monitoring by physicians.

Visual Field Testing Frequency and Associations in Children with Glaucoma.

PRCIS: Children with glaucoma had an average of 1.3 visual field tests per year. Self-reported black and multiracial patients had lower visual field testing rates, while older children with better visual acuity had more frequent testing. PURPOSE: To evaluate frequency of visual field (VF) testing in children with glaucoma and identify characteristics associated with VF frequency. METHODS: Retrospective cohort study of 82 children aged 6-18 years with glaucoma seen between August 2018-May 2023. Patients were divided into those who had ≥1 VF test (303 VF tests of 61 children) and 0 VFs (21 children). Eyes were excluded if best corrected visual acuity (BCVA) was counting fingers or worse. Characteristics obtained included age, self-reported race and ethnicity, sex, primary language, glaucoma diagnosis, distance to provider, office visit frequency, follow-up compliance, insurance type, and BCVA. The main outcome measure was VF testing frequency. RESULTS: Among children with ≥1 VF test, mean age at first VF was 11.8±2.8 years, mean number of VF/year was 1.3±0.8, and 44.9% of all VFs were reliable. 39.3% of patients underwent <1 VF/year, 45.9% ≥1 to <2 VFs/year, and 14.8% ≥2 VF/year. Children that were Black or multiracial had significantly lower VF testing frequency (estimated difference (ED) -1.2 [95% CI -2.0 to -0.4, P=0.002] and ED -1.3 [CI -2.2 to -0.3, P=0.008], respectively). Better visual acuity and greater office visit frequency were significantly associated with higher VF testing frequency (ED 0.052 [95% CI 0.001 to 0.103, P=0.045] and ED 0.2 [95% CI 0.1 to 0.3, P<0.001], respectively). CONCLUSIONS: Most children had between 1-2 VF/year, though less than half of all VFs were reliable. Ophthalmologists should consider barriers to care in glaucoma monitoring.

Factors associated with visual field testing reliability in children with glaucoma or suspected glaucoma.

PURPOSE: To evaluate Humphrey Visual Field (HVF) test reliability and its associated risk factors in children with glaucoma or glaucoma suspect. DESIGN: Retrospective cohort study. METHODS: None SETTING: Single-center childhood glaucoma clinic. PATIENT POPULATION: 136 patients aged ≤18 years with glaucoma/glaucoma suspect, and least 1 completed 24-2 HVF test between 2018 and 2023. OBSERVATION PROCEDURE: Demographic and clinical characteristics including age, primary language, visual acuity (VA), and glaucoma diagnosis were extracted from electronic health records. MAIN OUTCOME MEASURES: HVF 24-2 testing metrics, including FP, FN, and FL. Tests were defined as reliable using manufacturer guidelines of ≤33% FP, ≤33% FN, and ≤20% FL. For each patient, a reliability score was calculated as the percentage of reliable tests among all tests completed. A multivariable logistic regression model was used to determine factors associated with test-level reliability (yes/no). A multivariable linear regression model was used to determine factors associated with patient-level reliability score. RESULTS: Among 634 HVFs from 136 patients (Mean±SD age at first test 12.0±3.2 years, 47.8% female), 51.3% were reliable. Older age, better baseline VA, and English as primary language were associated with greater odds of test-level reliability (p<0.04). Mean±SD patient-level reliability score was 51.7±38.1%. Older age at first clinic visit, better baseline VA, and English as primary language were associated with higher reliability scores (all p<0.02), and number of prior VF tests was not (p=0.56). CONCLUSIONS: Younger age, worse visual acuity, and non-English as primary language were associated with decreased reliability and should be considered when interpreting VF testing in children. A significant learning effect was not observed with repeated testing.

Comparison of Brn3a and RBPMS Labeling to Assess Retinal Ganglion Cell Loss During Aging and in a Model of Optic Neuropathy.

Purpose: Retinal ganglion cell (RGC) loss provides the basis for diagnosis and stage determination of many optic neuropathies, and quantification of RGC survival is a critical outcome measure in models of optic neuropathy. This study examines the accuracy of manual RGC counting using two selective markers, Brn3a and RBPMS. Methods: Retinal flat mounts from 1- to 18-month-old C57BL/6 mice, and from mice after microbead (MB)-induced intraocular pressure (IOP) elevation, are immunostained with Brn3a and/or RBPMS antibodies. Four individuals masked to the experimental conditions manually counted labeled RGCs in three copies of five images, and inter- and intra-person reliability was evaluated by the intraclass correlation coefficient (ICC). Results: A larger population (approximately 10% higher) of RGCs are labeled with RBPMS than Brn3a antibody up to 6 months of age, but differences decrease to approximately 1% at older ages. Both RGC-labeled populations significantly decrease with age. MB-induced IOP elevation is associated with a significant decrease of both Brn3a- and RBPMS-positive RGCs. Notably, RGC labeling with Brn3a provides more consistent cell counts than RBPMS in interpersonal (ICC = 0.87 to 0.11, respectively) and intra-personal reliability (ICC = 0.97 to 0.66, respectively). Conclusions: Brn3a and RBPMS markers are independently capable of detecting significant decreases of RGC number with age and in response to IOP elevation despite RPBMS detecting a larger number of RGCs up to 6 months of age. Brn3a labeling is less prone to manual cell counting variability than RBPMS labeling. Overall, either marker can be used as a single marker to detect significant changes in RGC survival, each offering distinct advantages.

Early Single-Examination Optical Coherence Tomography Biomarkers for Treatment-Requiring Retinopathy of Prematurity.

Purpose: Optical coherence tomography (OCT) is an emerging adjunct imaging modality to evaluate retinopathy of prematurity (ROP). From an 11-year research database, we identify early OCT biomarkers that predict treatment-requiring ROP (TR-ROP). Methods: For preterm infants with acceptable OCT images at 32 ± 1 weeks postmenstrual age (PMA), we extracted the following measures: total retina, inner retinal layer (IRL), and outer retinal layer (ORL) thicknesses at the fovea and the parafovea, inner nuclear layer (INL) and choroidal thickness, parafovea/fovea (P/F) ratio, and presence of macular edema. Using univariable and multivariable logistic regression models, we evaluated the association between retinal and choroidal OCT measurements at 32 ± 1 weeks PMA and development of TR-ROP. Results: Of 277 eyes (145 infants) with usable OCT images, 67 eyes had TR-ROP. Lower P/F ratio (P < 0.0001), thicker foveal IRL (P = 0.0001), and thinner choroid (P = 0.03) were associated with TR-ROP in univariable analysis, but lost significance of association when adjusted for gestational age and race. Absence of macular edema was associated with TR-ROP when adjusted for gestational age and race (P = 0.01). In 185 eyes without macular edema, P/F ratio was associated with TR-ROP in both univariable analysis (P < 0.0001) and multivariable analysis (P = 0.02) with adjustment for gestational age and race. Conclusions: Presence of macular edema at 32 ± 1 weeks PMA in infants with lower gestational age may be protective against TR-ROP. In infants without macular edema, P/F ratio may be an early OCT biomarker for development of TR-ROP. Incorporation of early OCT biomarkers may be useful in prediction of TR-ROP.

Factors associated with outcomes of suprachoroidal hemorrhage: an individual participant data systematic review.

PURPOSE: To determine factors associated with visual and anatomic outcomes of suprachoroidal hemorrhage (SCH) in studies published between 1990 and 2022. METHODS: Individual participant data (IPD) systematic review. The protocol was prospectively registered on Open Science Framework (https://osf.io/69v3q/). PubMed, EMBASE, Web of Science, and Google Scholar were searched for peer-reviewed studies of SCH with ≥3 patients published between January 1, 1990, and September 1, 2022. The primary outcome was the change in logarithm of the minimum angle of resolution (logMAR) visual acuity (VA) from the time of SCH diagnosis to last follow-up. RESULTS: 413 eyes from 49 studies were included, with mean (SD) age 60.8 (22.4) years and mean (SD) follow-up of 13.8 (12.6) months. Among 145 eyes with at least 6 months of follow-up, the mean (SD) gain in VA was -0.98 (0.89) logMAR. In multivariable regression, treatment with systemic steroids was associated with greater improvement in logMAR VA (adjusted mean (SE) -1.29 (0.09) versus -0.16 (0.30) for no systemic steroids; P < 0.001) and greater odds of achieving anatomic success (adjusted OR 10.59, 95% CI 2.59 to 43.3; P = 0.001). CONCLUSIONS: The use of systemic steroids was associated with better visual and anatomic outcomes for SCH.

Stimulus type and duration affect magnitude and evolution of flicker-induced hyperemia measured by laser speckle flowgraphy at the optic disc and peripapillary vessels.

Neurovascular coupling is a vital mechanism employed by the cerebrovascular system, including the eye, to regulate blood flow in periods of neuronal activation. This study aims to investigate if laser speckle flowgraphy (LSFG) can detect coupling response elicited by flickering light stimuli and how variations in stimulus type and duration can affect the magnitude and evolution of blood flow in the optic nerve head (ONH) and peripapillary vessels. Healthy adults were exposed to two types of 10-Hz flicker stimuli: a photopic negative response-like stimulus (PhNR-S) or a visual evoked potential-like stimulus (VEP-S)-each presented in separate 10- and 60-s epochs. Both PhNR-S and VEP-S significantly increased ONH blood flow (p < 0.001) immediately after flicker cessation, with a trend of 60-s stimuli (PhNR-S = 11.6%; VEP-S = 10.4%) producing a larger response than 10-s stimuli (PhNR-S = 7.5%; VEP-S = 6.2%). Moreover, exposure to 60-s stimuli elicited a significantly prolonged ONH hyperemic response, especially with PhNR-S. Lastly, stimulation with either 60-s stimuli elicited a robust increase in blood flow within the peripapillary arterioles (p < 0.01) and venules (p < 0.01) as well. Flicker stimulation with common visual electrophysiology stimuli (PhNR-S and VEP-S) induced a demonstrable increase in ONH and peripapillary vessel blood flow, which varied with flicker duration. Our results validate that LSFG is a robust method to quantify flicker-induced hyperemic responses and to study neurovascular coupling in humans.

Association between systemic medication use and severity of dry eye signs and symptoms in the DRy eye assessment and management (DREAM) study.

PURPOSE: Some systemic medications are reported to be associated with dry eye disease (DED), yet their associations with the severity of DED signs and symptoms are not well studied. To evaluate these associations, we performed a secondary analysis of data from the DRy Eye Assessment and Management (DREAM) Study. METHODS: Participants (N = 535) were assessed for DED signs using tear break-up time (TBUT), Schirmer testing, corneal fluorescein staining, conjunctival lissamine green staining, meibomian gland dysfunction (MGD), and tear osmolarity and DED symptoms using the Ocular Surface Disease Index (OSDI). We derived a composite signs severity score from the 6 DED signs and categorized participant-reported systemic medications into antidepressants, antihistamines, aspirin, corticosteroids, diuretics, nonsteroidal anti-inflammatory drugs, proton pump inhibitors, statins, vitamin D3, and medications for diabetes mellitus, hypertension, hypothyroidism, migraine, and seizure. Generalized linear models were used to compare DED symptom and sign scores between medication users and non-users, with adjustment for factors associated with DED severity. RESULTS: Compared to non-users, antihistamine users had lower TBUT (p = 0.01) and higher OSDI score (p = 0.02); aspirin users had lower TBUT (p = 0.02); corticosteroid users had lower TBUT (p = 0.02), lower Schirmer test scores (p = 0.03), higher cornea fluorescein staining (p = 0.01), higher composite severity score (p = 0.01), and higher OSDI score (p = 0.03); seizure medication users had higher composite severity score (p = 0.02); vitamin D3 users had lower TBUT (p = 0.001) and greater MGD (p = 0.03); and diuretic users had less MGD (p = 0.03). CONCLUSIONS: Certain systemic medications may be associated with more severe DED. This may guide prescription practices in patients with DED.

A Prospective Study of the Effects of General Anesthesia on Intraocular Pressure in Healthy Children.

Purpose: To determine the effect of general anesthesia on intraocular pressure (IOP) in children with no intraocular pathology and determine which postanesthetic time point is most predictive of preinduction IOP. Design: Prospective observational study. Participants: Children with no intraocular pathology ≤ 18 years scheduled for general anesthesia as part of their routine care followed by a pediatric ophthalmologist at Nanjing Medical University. Methods: Participants underwent a standardized general anesthetic protocol using a mask induction with sevoflurane and propofol maintenance. Intraocular pressure was measured at the following 7 time points: preinduction (taken in the preoperative area), postinduction minutes 1, 3, and 5, and postairway placement minutes 1, 3, and 5 for a total time period of 10 minutes after induction. A generalized estimating equation was used to evaluate the effect of anesthesia on IOP and the effect of patient factors (age, gender, vital signs, and airway type) on preanesthetic and postanesthetic IOP. An IOP prediction model was developed using the postanesthesia IOP measurements for predicting preinduction IOP. Main Outcome Measures: Intraocular pressure and change in IOP at prespecified time points. Results: Eighty-five children were enrolled with a mean ± standard deviation (SD) age of 7.5 ± 2.9 years. Mean ± SD preinduction IOP was 20.1 ± 3.7 mmHg. Overall, IOP was lowest at 3 minutes postinduction, decreased to a mean of 13.4 ± 3.7 mmHg (P < 0.001). After this, IOP rose 5 minutes postinduction to 16.5 ± 4.2 mmHg, which did not reach preinduction IOP levels (P < 0.001). The IOP prediction model showed that combining 1 minute postinduction and 3 minutes postairway was most predictive (R2 = 0.13), whereas 1 minute postairway was least predictive of preinduction IOP (R2 = 0.01). Conclusions: After the induction of general anesthesia in children, IOP temporarily decreases with a trough at 3 minutes postinduction before increasing and remaining stable just below preinduction levels. Intraocular pressure measurements taken 1 minute after induction with 3 minutes after airway placement are most predictive of preinduction IOP, though predictive value is relatively low. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Two-Year Progression of Dry Eye Disease in Dry Eye Assessment and Management Study.

PURPOSE: The purpose of this study was to evaluate the progression of dry eye disease (DED) symptoms and signs over 2 years through a secondary analysis of data collected from the Dry Eye Assessment and Management study. METHODS: Participants who were assigned to omega-3 fatty acid in the first year were rerandomized in the second year to either continue with omega-3 fatty acid or switch to placebo. At baseline, 3, 6, 12, 18, and 24 months, DED symptoms were evaluated by using the Ocular Surface Disease Index and the Brief Ocular Discomfort Index (BODI). DED signs were assessed using conjunctival staining, corneal staining, tear break-up time, Schirmer testing, and keratography measures. Medication usage was documented at each visit. Because the treatment and placebo groups displayed no statistical differences in both signs and symptoms, data from the 43 participants were combined to assess longitudinal changes in symptoms and signs. RESULTS: At 3 months after omega-3 fatty acid treatment, there were significant improvements from baseline in Ocular Surface Disease Index and Brief Ocular Discomfort Index scores (all P ≤ 0.002) and less use of artificial tears or gel (P = 0.02), but between 3 and 24 months, no significant changes in symptoms and treatments were observed (P ≥ 0.06). Except for a significant improvement in conjunctival staining score over 2 years (P = 0.001), there were no significant sign changes in corneal staining (P = 0.32), tear break-up time (P = 0.43), Schirmer test (P = 0.09), and additional measures (all P ≥ 0.07). CONCLUSIONS: We did not observe a progression of DED signs or symptoms over a 2-year period, except for a probable placebo response in symptoms in the first 3 months and an improvement in conjunctival staining score.

Association of Systemic Markers of Inflammation with Signs and Symptoms of Dry Eye Disease and Sjogren's Syndrome in the Dry Eye Assessment and Management (DREAM©) Study.

PURPOSE: To evaluate the possible role of systemic inflammation in dry eye disease (DED) via systemic inflammatory marker associations with DED signs and symptoms, and an analysis of a subgroup with Sjogren's Syndrome (SS). METHODS: Participant serums were analyzed using line immunoassays (LIAs) for the presence of antibodies against 34 systemic inflammatory markers. Using the 2012 American College of Rheumatology definition, the 481 participants were categorized into group 1 (SS; n = 52), group 2 (autoimmune disease not including SS; n = 66), or group 3 (control, i.e. no autoimmune disease; n = 363). RESULTS: 3 markers were positive in ≥10% of participants: Ro52 (19.3%), Scl-70 (15.0%), CN-1A (14.2%). 2 markers were positively associated with symptoms: PM-Scl100 (p = 0.02), Sm (p = 0.009). 5 markers were positively associated with signs: U2SnRNP A', Ro52, La, DNA, Ro60. SS participants showed significantly higher positivity for 4 markers compared to participants with no autoimmune disease: PL-7 (p = 0.02), Ro52 (p < 0.0001), La (p < 0.0001), Ro60 (p < 0.0001). SS participants showed significantly higher positivity for 3 markers compared to participants with another autoimmune disease: Ro52 (p < 0.0001), La (p = 0.002), Ro60 (p < 0.0001). CONCLUSIONS: This study did not show evidence of significant systemic inflammation in participants with moderate-to-severe DED, based on the markers tested. PM-Scl100 and Sm may be associated with more severe DED symptoms. U2SnRNP A', Ro52, La, DNA, and Ro60 may be associated with more severe ocular surface disease. Ro52 and PL-7 may be diagnostic markers for SS. Future research evaluating these relationships and their clinical significance is needed.

The Relationship Between Choroidal Abnormalities and Visual Outcomes in Pediatric Patients With NF1-Associated Optic Pathway Gliomas.

BACKGROUND: Choroidal abnormalities (CAs) visualized on near-infrared reflectance (NIR) imaging are a new diagnostic criterion for neurofibromatosis type 1 (NF1), but the association between the presence of CAs and visual function remains unknown. This study evaluated the relationship between visual acuity (VA) with the presence, number, or total area of CAs visualized by NIR in children with NF1-associated optic pathway gliomas (NF1-OPGs). METHODS: Patients (<18 years) enrolled in a prospective longitudinal study of children with NF1-associated OPGs from 3 institutions were eligible if they had optical coherence tomography (OCT) of the macula (Heidelberg Spectralis) with ≥1 year of follow-up. The central 30° NIR images were reviewed by 2 neuro-ophthalmologists who manually calculated the number and total area of CAs. VA (logMAR) was measured using a standardized protocol. Cross-sectional associations of presence, number, and total area of CAs with VA, retinal nerve fiber layer thickness (RNFL), and ganglion cell-inner plexiform layer thickness were evaluated at the first and most recent visits using regression models. Intereye correlation was accounted for using generalized estimating equations. RESULTS: Eighty-two eyes of 41 children (56% female) were included. The mean ± SD age at the first OCT was 10.1 ± 3.3 years, with a mean follow-up of 20.4 ± 7.2 months. At study entry, CAs were present in 46% of eyes with a mean number of 2.1 ± 1.7 and a mean total area of 2.0 ± 1.7 mm 2 per eye. At the most recent follow-up, CAs were present in 48% of eyes with a mean number of 2.2 ± 1.8 lesions and a mean total area of 2.3 ± 2.1 mm 2 per eye. Neither VA nor OCT parameters at first and follow-up visits were associated with the presence, number, or total area of CAs (all P > 0.05). CONCLUSIONS: CAs are prevalent but not ubiquitous, in children with NF1-OPGs. Although CAs are a diagnostic criterion for NF1, their presence and size do not appear to be associated with visual function.

Effect of Lens Status on the Outcomes of Glaucoma Drainage Device Implantation.

PURPOSE: To assess the effect of lens status and cataract surgery on glaucoma drainage device (GDD) efficacy. DESIGN: Retrospective cohort study. PARTICIPANTS: Two hundred and forty-three eyes of 216 patients that underwent GDD implantation with ≥1 follow-up visit within 3 years postoperatively. Exclusion criteria included GDD combined with other ophthalmic procedures. 90%-94% of GDDs were Ahmed implants; 83%-90% had adjunctive mitomycin-C. METHODS: Outcomes were compared between phakic eyes (group A), eyes phakic at time of implantation but subsequently underwent cataract surgery within 3 years (group B), and pseudophakic eyes (group C). Outcomes were measured at 1, 3, 6, 12, 24, and 36 months after tube shunt implantation. Multivariable regression models were performed, adjusting for baseline characteristics. MAIN OUTCOME MEASURES: Intraocular pressure (IOP) after GDD implantation. Secondary outcomes included change in visual acuity (VA), number of glaucoma eye drops, and rate of failure, defined as additional glaucoma surgery, vision decrease to no light perception, or IOP persistently ≤ 5 mmHg or > 21 mmHg or not reduced from baseline by 20%. RESULTS: There were 65 eyes in group A, 52 in group B, and 126 in group C. Within group B, cataract surgery was performed at a mean of 1.3 ± 0.7 years after GDD implantation. There were no statistically significant differences in mean IOP or medications between the 3 groups at all time points up to 3 years postoperatively. Significant improvement in VA was noted in groups A and B compared to group C at 6 months, 1 year, and 2 years after implantation; however, by postoperative year 3, change in VA was similar across groups. There were no significant differences in the failure rate amongst groups (P = 0.68). IOP and medications up to 12 months after cataract surgery were similar compared to preoperative baseline. Group B had significantly more short-term (P = 0.02) and long-term (P < 0.001) postoperative complications than groups A or C, driven primarily by hypotony. CONCLUSIONS: There were no differences in IOP, glaucoma medications, or rate of failure 3 years after GDD implantation based on lens status or after undergoing subsequent cataract surgery. These results may inform the management of patients with co-existing glaucoma and cataract. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

A latent profile analysis of tear cytokines and their association with severity of dry eye disease in the Dry Eye Assessment and Management (DREAM) study.

This study is to identify subgroups of DED patients with different tear cytokine profiles and compare their DED symptoms and signs among subgroups. Baseline tear cytokines (IL-1ß, IL-6, IL-8, IL-10, IL-17A, IFN-γ and TNF-α) were measured using a magnetic bead assay. DED symptoms were assessed by Ocular Surface Disease Index (OSDI) and signs were assessed by corneal and conjunctival staining, tear break-up time (TBUT), Schirmer's test, tear osmolarity and meibomian gland dysfunction (MGD). Latent profile analysis was performed to identify subgroups, and their scores of DED symptoms and signs were compared using generalized linear regression. Among 131 patients with total tear volume > 4 µl from both eyes, subgroup 1 (n = 23) significantly higher in IL-6 and IL-8 (all p < 0.001) and subgroup 2 (n = 108) significantly higher in IL-10 (p = 0.03), IL-17A (p < 0.001), and IFN-γ (p < 0.001). Both subgroups were similar in demographics and DED symptoms, but subgroup 1 had significantly more severe DED signs: higher conjunctival staining (3.38 vs. 2.69, p = 0.04), corneal staining (4.26 vs. 3.03, p = 0.03), lower Schirmer's test score (8.20 vs. 13.72, p < 0.001), and higher composite severity score of DED sign (0.62 vs. 0.45, p = 0.002). We identified two DED subgroups with different profiles of tear cytokines. Patients in these subgroups differed significantly in DED signs, supporting the inflammation's role in DED development and progression.

The long and short of it: a comprehensive assessment of axial length estimation in myopic eyes from ocular and demographic variables.

BACKGROUND/OBJECTIVES: Axial length, a key measurement in myopia management, is not accessible in many settings. We aimed to develop and assess machine learning models to estimate the axial length of young myopic eyes. SUBJECTS/METHODS: Linear regression, symbolic regression, gradient boosting and multilayer perceptron models were developed using age, sex, cycloplegic spherical equivalent refraction (SER) and corneal curvature. Training data were from 8135 (28% myopic) children and adolescents from Ireland, Northern Ireland and China. Model performance was tested on an additional 300 myopic individuals using traditional metrics alongside the estimated axial length vs age relationship. Linear regression and receiver operator characteristics (ROC) curves were used for statistical analysis. The contribution of the effective crystalline lens power to error in axial length estimation was calculated to define the latter's physiological limits. RESULTS: Axial length estimation models were applicable across all testing regions (p ≥ 0.96 for training by testing region interaction). The linear regression model performed best based on agreement metrics (mean absolute error [MAE] = 0.31 mm, coefficient of repeatability = 0.79 mm) and a smooth, monotonic estimated axial length vs age relationship. This model was better at identifying high-risk eyes (axial length >98th centile) than SER alone (area under the curve 0.89 vs 0.79, respectively). Without knowing lens power, the calculated limits of axial length estimation were 0.30 mm for MAE and 0.75 mm for coefficient of repeatability. CONCLUSIONS: In myopic eyes, we demonstrated superior axial length estimation with a linear regression model utilising age, sex and refractive metrics and showed its clinical utility as a risk stratification tool.

INCIDENCE AND RISK FACTORS FOR EXUDATIVE RETINAL DETACHMENT FOLLOWING LASER PHOTOCOAGULATION FOR RETINOPATHY OF PREMATURITY.

PURPOSE: Exudative retinal detachment (ERD) may result from laser photocoagulation for retinopathy of prematurity. Although risk factors have been hypothesized from case reports, comparative studies have not been reported. We sought to evaluate risk factors for ERD following laser, comparing affected and unaffected infants. METHODS: Retrospective cohort study of infants undergoing retinopathy of prematurity laser at the Children's Hospital of Philadelphia over 6 years. All received near-confluent laser of avascular retina. Demographic, medical, and procedural risk factors for ERD were evaluated in univariate analysis because of the rarity of ERD. RESULTS: Among 149 lasered infants, 6 infants (4%, 95% confidence interval [CI] 1.5%-8.6%) developed ERD. Race was a significant risk factor ( P = 0.01). Among 71 African American or Hispanic infants, 6 (8.5%, 95% CI 3.2%-17.5%) developed ERD. Among 78 non-African American or Hispanic infants, 0 (0%, 95% CI 0%-4.6%) developed ERD. There were no significant differences in the other studied factors. CONCLUSION: Exudative retinal detachment was uncommon (4%) following retinopathy of prematurity laser. Despite so few cases, darker pigmented race with likely increased pigmented fundi was significantly associated with an increased ERD risk. Further study may reveal whether increased choroidal pigment causes greater laser tissue damage or makes it difficult to discern the ora, resulting in inadvertent lasering of the ciliary body, leading to ERD.

Long-term visual acuity outcomes following cataract surgery in eyes with ocular inflammatory disease.

PURPOSE: To evaluate the long-term visual acuity (VA) outcome of cataract surgery in inflammatory eye disease. SETTING: Tertiary care academic centres. DESIGN: Multicentre retrospective cohort study. METHODS: A total of 1741 patients with non-infectious inflammatory eye disease (2382 eyes) who underwent cataract surgery while under tertiary uveitis management were included. Standardised chart review was used to gather clinical data. Multivariable logistic regression models with adjustment for intereye correlations were performed to evaluate the prognostic factors for VA outcomes. Main outcome measure was VA after cataract surgery. RESULTS: Uveitic eyes independent of anatomical location showed improved VA from baseline (mean 20/200) to within 3 months (mean 20/63) of cataract surgery and maintained through at least 5 years of follow-up (mean 20/63). Eyes that achieved 20/40 or better VA at 1 year were more likely to have scleritis (OR=1.34, p<0.0001) or anterior uveitis (OR=2.2, p<0.0001), VA 20/50 to 20/80 (OR 4.76 as compared with worse than 20/200, p<0.0001) preoperatively, inactive uveitis (OR=1.49, p=0.03), have undergone phacoemulsification (OR=1.45 as compared with extracapsular cataract extraction, p=0.04) or have had intraocular lens placement (OR=2.13, p=0.01). Adults had better VA immediately after surgery, with only 39% (57/146) paediatric eyes at 20/40 or better at 1 year. CONCLUSIONS: Our results suggest that adult and paediatric eyes with uveitis typically have improved VA following cataract surgery and remain stable thereafter for at least 5 years.

Association of Tear Cytokine Ratios with Symptoms and Signs of Dry Eye Disease: Biomarker Data from the Dry Eye Assessment and Management Study.

PURPOSE: To assess the relationship between tear inflammatory cytokine ratios (CRs) and signs and symptoms of dry eye disease (DED) to investigate the possible use of tear CRs, which may better address the complexity of cytokine interactions than absolute cytokine levels, as a DED biomarker. METHODS: Tear concentrations of IL-1b, IL-6, IL-8, IL-10, IL-17A, IFN-g, and TNF-a were measured using standardized procedures, as were DED signs (corneal and conjunctival staining scores, tear break-up time, Schirmer test, Meibomian gland plugging, tear osmolarity, composite sign severity score) and symptoms [Ocular Surface Disease Index (OSDI)]. Ratios between pro-inflammatory (IL-1b, IL-8, IL-17A, IFN-g, and TNF-a) and anti-inflammatory (IL-10) cytokines were calculated. Given its opposing roles in inflammation, IL-6 was tested as both a pro- and anti-inflammatory cytokine. Correlations between CR and DED symptoms and signs were calculated using Spearman correlation coefficients (rho). RESULTS: At baseline, 131 patients, 80.2% female and mean age 54.2 years (SD 14.1, range 20-82), from 10 sites of the Dry Eye Assessment and Management study had sufficient tear volumes ≥4 µL for analysis. IL-6:IL-10, IL-8:IL-10, and TNF-a:IL-10 had some significant correlations, mostly with conjunctival or corneal staining or the composite sign severity score (IL-8:IL-10 and conjunctival staining: rho = 0.19, p = 0.03; IL-6:IL-10 and corneal staining: rho = 0.31, p < 0.001; IL-8:IL-10 and corneal staining: rho = 0.21, p = 0.01; IL-6:IL-10 and composite sign severity score: rho = 0.26, p = 0.003; IL-8:IL-10 and composite sign severity score: rho = 0.26, p = 0.003; TNF-a:IL-10 and corneal staining: rho = 0.29, p < 0.001; TNF-a:IL-10 and Schirmer test: rho = -0.23, p = 0.009). CRs had no significant correlation with DED symptoms. All significant correlations using IL-6 in the denominator (anti-inflammatory) produced counterintuitive results based on clinical understanding of the disease. CONCLUSIONS: Pro- to anti-inflammatory CR was weakly correlated with some DED signs and not with symptoms, as measured by OSDI. Future studies in different dry eye populations are needed and should address sampling biases and tear collection techniques.

Longitudinal Choroidal Development in Preterm Infants.

Purpose: To characterize changes in subfoveal choroidal thickness in preterm infants from 30 to 60 weeks' postmenstrual age (PMA). Design: The prospective, observational Study of Eye Imaging in Preterm infantS (BabySTEPS) enrolled infants eligible for retinopathy of prematurity screening per the American Association of Pediatrics guidelines. Subjects: Infants imaged with an investigational, handheld OCT at ≥ 4 distinct imaging sessions between 30 to 60 weeks' PMA as part of BabySTEPS. Methods: Average choroidal thickness across the central subfoveal 1 mm in each eye at each time point was measured using custom segmentation software, and errors were manually corrected by a trained grader. We prospectively collected birth history data. A segmented mixed model was used to analyze the change in choroidal thickness as a function of PMA, birth weight, and gestational age (GA). Main Outcome Measures: Characterization of normative subfoveal choroidal thickness values and choroidal growth rate between 30 to 60 weeks' PMA. Results: We included 592 imaging sessions of 79 preterm infants (152 eyes). Mean (± standard deviation) GA was 27.5 ± 2.5 weeks. Mean choroidal thickness was 141.4 ± 34.5 µm at 30 weeks, 272.2 ± 83.9 µm at 38 weeks, and 306.2 ± 77.4 µm between 56 and 60 weeks. Between 30 and 60 weeks' PMA, choroidal growth followed a biphasic model, with a linear growth rate of 14.8 µm per week (95% confidence interval [CI], 13.6-16.0) from 30 until 38.4 weeks, then cessation of growth, with a growth rate of 0.3 µm per week (95% CI, -1.1 to 1.6) from 38.4 to 60 weeks. Infants with extremely low birth weight (ELBW; < 1000 g) and extremely preterm (GA < 28 weeks) infants had significantly slower initial growth rates compared with very low and low birth weight and very preterm and preterm infants (ELBW 13.0 vs. 21.0 µm per week; P < 0.0001 and extremely preterm 13.2 vs. 18.0 µm per week; P = 0.003). Conclusions: Preterm infant choroidal thickness experiences rapid linear growth from 30 to 38 weeks' PMA, at which time growth nearly stops. These foundational measurements and identification of the impact of extremes of low birth weight and prematurity on choroidal development will be essential as researchers begin to understand the role of choroidal development in ocular and retinal health in human infants. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Deep Learning-Facilitated Study of the Rate of Change in Photoreceptor Outer Segment Metrics in RPGR-Related X-Linked Retinitis Pigmentosa.

Purpose: The aim of this retrospective cohort study was to obtain three-dimensional (3D) photoreceptor outer segment (OS) metrics measurements with the assistance of a deep learning model (DLM) and to evaluate the longitudinal change in OS metrics and associated factors in retinitis pigmentosa GTPase regulator (RPGR) X-linked retinitis pigmentosa (XLRP). Methods: The study included 34 male patients with RPGR-associated XLRP who had preserved ellipsoid zone (EZ) within their spectral-domain optical coherence tomography volume scans and an approximate 2-year or longer follow-up. Volume scans were segmented using a DLM with manual correction for EZ and apical retinal pigment epithelium (RPE). OS metrics were measured from 3D EZ-RPE layers of volume scans. Linear mixed-effects models were used to calculate the rate of change in OS metrics and the associated factors, including baseline age, baseline OS metrics, and follow-up duration. Results: The mean (standard deviation) of progression rates were -0.28 (0.43) µm/y, -0.73 (0.61) mm2/y, and -0.014 (0.012) mm3/y for OS thickness, EZ area, and OS volume, respectively. In multivariable analysis, the progression rates of EZ area and OS volume were strongly associated with their baseline values, with faster decline in eyes with larger baseline values (P ≤ 0.003), and nonlinearly associated with the baseline age (P ≤ 0.003). OS thickness decline was not associated with its baseline value (P = 0.32). Conclusions: These results provide evidence to support using OS metrics as biomarkers to assess the progression of XLRP and as the outcome measures of clinical trials. Given that their progression rates are dependent on their baseline values, the baseline EZ area and OS volume should be considered in the design and statistical analysis of future clinical trials. Deep learning may provide a useful tool to reduce the burden of human graders to analyze OCT scan images and to facilitate the assessment of disease progression and treatment trials for retinitis pigmentosa.