P Score: A Reference Image-Based Clinical Grading Scale for Vascular Change in Retinopathy of Prematurity.

PURPOSE: The International Classification of Retinopathy of Prematurity, Third Edition (ICROP3), acknowledged that plus-like retinopathy of prematurity (ROP) vascular changes occurs along a spectrum. Historically, clinician-experts demonstrate variable agreement for plus diagnosis. We developed a 9-photograph reference image set for grading plus-like changes and compared intergrader agreement of the set with standard grading with no plus, preplus, and plus disease. DESIGN: Retinal photographic grading and expert consensus opinion. PARTICIPANTS: The development set included 34 international ICROP3 committee members. The validation set included 30 ophthalmologists with ROP expertise (15 ICROP3 committee members and 15 non-ICROP3 members) METHODS: Nine ROP fundus images (P1 through P9) representing increasing degrees of zone I vascular tortuosity and dilation, based on the 34 ICROP3 committee members' gradings and consensus image reviews, were used to establish standard photographs for the plus (P) score. Study participants graded 150 fundus photographs 2 ways, separated by a 1-week washout period: (1) no plus, preplus, or plus disease and (2) choosing the closest P score image. MAIN OUTCOME MEASURES: Intergrader agreement measured by intraclass correlation coefficient. RESULTS: Intergrader agreement was higher using the P score (intraclass correlation coefficient, 0.75; 95% confidence interval, 0.71-0.79) than no plus, preplus, or plus disease (intraclass correlation coefficient, 0.67; 95% confidence interval, 0.62-0.72). Mean ± standard deviation P scores for images with mode gradings of no plus, preplus, and plus disease were 2.5 ± 0.7, 4.8 ± 0.8, and 7.4 ± 0.8, respectively. CONCLUSIONS: Intergrader agreement of plus-like vascular change in ROP using the P score is high. We now incorporate this 9-image reference set into ICROP3 for use in clinician daily practice alongside zone, stage, and plus assessment. P score is not yet meant to replace plus diagnosis for treatment decisions, but its use at our institutions has permitted better comparison between examinations for progression and regression, communication between examiners, and documentation of vascular change without fundus imaging. P score also could provide more detailed ROP classification for clinical trials, consistent with the spectrum of plus-like change that is now formally part of the International Classification of Retinopathy of Prematurity. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

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.

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 in studies published between 1990 and 2022. METHODS: Individual participant data 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 suprachoroidal hemorrhage 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 visual acuity from the time of suprachoroidal hemorrhage diagnosis to last follow-up. RESULTS: Four hundred thirteen 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 visual acuity was -0.98 (0.89) logarithm of the minimum angle of resolution. In multivariable regression, treatment with systemic steroids was associated with greater improvement in logarithm of the minimum angle of resolution visual acuity (adjusted mean [SE] -1.29 [0.09] vs. -0.16 [0.30] for no systemic steroids; P < 0.001) and greater odds of achieving anatomic success (adjusted OR 10.59, 95% confidence interval 2.59-43.3; P = 0.001). CONCLUSION: The use of systemic steroids was associated with better visual and anatomic outcomes for suprachoroidal hemorrhage.

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.

Lacrimal Obstruction in Craniosynostosis: Anatomical and Genetic Risk Factors.

PURPOSE: To investigate whether patients with craniosynostosis exhibit higher rates of nasolacrimal duct obstruction (NLDO) and to explore potential risk factors. METHODS: Retrospective review including all craniosynostosis patients treated at both the Divisions of Ophthalmology and Plastic, Reconstructive, and Oral Surgery at The Children's Hospital of Philadelphia between 2009 and 2020 was conducted. Synostosis characteristics, lacrimal disorders, and genetic data were collected. Main outcome measures were the rate of NLDO and associations with anatomical and syndromic/genetic risk factors. RESULTS: The total of 767 participants had a mean age of 2.8 ± 3.8 years, 465 (60.6%) were males, 485 (63.2%) had no syndromic association; 631 (82.3%) had one major suture involved, 128 (17%) had involvement of 2 to 4 major sutures, and 429 (55.9%) underwent craniofacial surgery. Forty-eight (6.2%) patients had NLDO, which more prevalent in the genetic/syndromic group (11.0% vs. 3.5%, respectively, p < 0.001), with the highest prevalence observed in patients with Apert syndrome (n = 4, 30.8%). The genetic variants most associated with NLDO were EFNB1 (n = 1, 100%) and FGFR2 (n = 6, 19.4%). There was no association between NLDO and the number or types of sutures involved or a history of craniofacial surgery. CONCLUSIONS: Nasolacrimal duct obstruction is more common in patients with craniosynostosis compared to the general population. Having a putative syndrome or a putative genetic variant and female sex were risk factors for NLDO. Ophthalmic evaluations for all craniosynostosis patients and careful assessments of any symptoms of tearing are recommended.

Prescribing patterns for paediatric hyperopia among paediatric eye care providers.

PURPOSE: To survey paediatric eye care providers to identify current patterns of prescribing for hyperopia. METHODS: Paediatric eye care providers were invited, via email, to participate in a survey to evaluate current age-based refractive error prescribing practices. Questions were designed to determine which factors may influence the survey participant's prescribing pattern (e.g., patient's age, magnitude of hyperopia, patient's symptoms, heterophoria and stereopsis) and if the providers were to prescribe, how much hyperopic correction would they prescribe (e.g., full or partial prescription). The response distributions by profession (optometry and ophthalmology) were compared using the Kolmogorov-Smirnov cumulative distribution function test. RESULTS: Responses were submitted by 738 participants regarding how they prescribe for their hyperopic patients. Most providers within each profession considered similar clinical factors when prescribing. The percentages of optometrists and ophthalmologists who reported considering the factor often differed significantly. Factors considered similarly by both optometrists and ophthalmologists were the presence of symptoms (98.0%, p = 0.14), presence of astigmatism and/or anisometropia (97.5%, p = 0.06) and the possibility of teasing (8.3%, p = 0.49). A wide range of prescribing was observed within each profession, with some providers reporting that they would prescribe for low levels of hyperopia while others reported that they would never prescribe. When prescribing for bilateral hyperopia in children with age-normal visual acuity and no manifest deviation or symptoms, the threshold for prescribing decreased with age for both professions, with ophthalmologists typically prescribing 1.5-2 D less than optometrists. The threshold for prescribing also decreased for both optometrists and ophthalmologists when children had associated clinical factors (e.g., esophoria or reduced near visual function). Optometrists and ophthalmologists most commonly prescribed based on cycloplegic refraction, although optometrists most commonly prescribed based on both the manifest and cycloplegic refraction for children ≥7 years. CONCLUSION: Prescribing patterns for paediatric hyperopia vary significantly among eye care providers.

Association of Surgical Necrotizing Enterocolitis and Its Timing with Retinopathy of Prematurity.

OBJECTIVE: The study aimed to determine the association of surgical necrotizing enterocolitis (NEC) and its timing, with the development and timing of retinopathy of prematurity (ROP). STUDY DESIGN: This was a secondary data analysis of 7,483 preterm infants from the Postnatal Growth and Retinopathy of Prematurity Study. Associations between infants with surgical NEC, early-onset surgical NEC (8-28 days), and late-onset surgical NEC (over 28 days) with ROP were evaluated by using multivariable logistic regression models, controlling for birth weight, gestational age, small for gestational age status, chronic lung disease, intraventricular hemorrhage, hydrocephalus, patent ductus arteriosus, and periventricular leukomalacia. RESULTS: Three hundred fifty-six (4.8%) infants had surgical NEC, with 56% having early surgical NEC. Infants with surgical NEC had a higher risk of any ROP and severe ROP (adjusted odds ratio [OR]: 2.7; 95% CI: 1.9-3.7) and 2.5 (95% CI: 1.9-3.3), respectively; p < 0.001) compared with infants without surgical NEC. Infants with early surgical NEC were at the highest risk of developing ROP and severe ROP (adjusted OR: 3.1 [95% CI: 2.1-4.8], and 3.3 [95% CI: 2.3-4.7] respectively, p < 0.001). Infants with late surgical NEC were also at increased risk of developing ROP and severe ROP (adjusted OR: 2.1 [95% CI: 1.3-3.4], and 1.9 [95% CI: 1.3-2.8] respectively, p < 0.001) compared with infants without surgical NEC. CONCLUSION: Infants with surgical NEC, especially early surgical NEC, are at higher risk of ROP and severe ROP. KEY POINTS: · Infants with surgical NEC are at higher risk of ROP and severe ROP than those without surgical NEC.. · Increased ROP risk is seen in infants with both early- or later onset surgical NEC.. · Early-onset surgical NEC is associated with a higher ROP risk compared with later onset surgical NEC..

Outcome of Primary Monocanalicular Stent Placement in Pediatric Down Syndrome Patients with Congenital Nasolacrimal Obstruction.

PURPOSE: Congenital Nasolacrimal duct obstruction (CNLDO) is a relatively common problem in children with Down syndrome (DS). Probing and irrigation (PI) with monocanalicular stent intubation may be less successful than in non-DS patients, thus raising some concerns regarding the preferred treatment in this population. We aimed to analyze the surgical outcome of PI along with monocanalicular stent intubation in children with DS compared with non-DS patients. METHODS: Retrospective cohort study. Thirty-five eyes of 19 children with DS and 1,472 eyes of 1,001 children without DS underwent PI-monocanalicular stent intubation as a primary treatment for CNLDO. All patients were operated on by a single surgeon at the Children's Hospital of Philadelphia between 2009 and 2020. The main outcome measure was a surgical success, defined as the resolution of symptoms after surgery. RESULTS: A total of 1,020 patients were included, 48% females; mean age of 1.9 ± 1.4 years. The mean follow-up time was 35.0 months. The DS patients group consisted of 19 patients. Higher rates of right nasolacrimal duct obstruction and bilateral obstructions were observed in the DS group (100% vs. 73.2%; p = 0.006, and 84.2% vs. 46.8%; p = 0.001, respectively). Patients with DS had a lower success rate (57.1% vs. 92.4%; p < 0 .0001). The median time to failure was 3.1 months in the DS group, and 5.2 months in the group of patients without DS. The hazard ratio comparing DS to the no-DS outcome was 6.6 (95% CI: 3.2-13.7; p < 0.001). CONCLUSIONS: CNLDO in DS is more likely to be bilateral and less likely to resolve after primary monocanalicular stent placement.

Estimation and testing for clustered interval-censored bivariate survival data with application using the semi-parametric version of the Clayton-Oakes model.

The Kaplan-Meier estimator is ubiquitously used to estimate survival probabilities for time-to-event data. It is nonparametric, and thus does not require specification of a survival distribution, but it does assume that the risk set at any time t consists of independent observations. This assumption does not hold for data from paired organ systems such as occur in ophthalmology (eyes) or otolaryngology (ears), or for other types of clustered data. In this article, we estimate marginal survival probabilities in the setting of clustered data, and provide confidence limits for these estimates with intra-cluster correlation accounted for by an interval-censored version of the Clayton-Oakes model. We develop a goodness-of-fit test for general bivariate interval-censored data and apply it to the proposed interval-censored version of the Clayton-Oakes model. We also propose a likelihood ratio test for the comparison of survival distributions between two groups in the setting of clustered data under the assumption of a constant between-group hazard ratio. This methodology can be used both for balanced and unbalanced cluster sizes, and also when the cluster size is informative. We compare our test to the ordinary log rank test and the Lin-Wei (LW) test based on the marginal Cox proportional Hazards model with robust standard errors obtained from the sandwich estimator. Simulation results indicate that the ordinary log rank test over-inflates type I error, while the proposed unconditional likelihood ratio test has appropriate type I error and higher power than the LW test. The method is demonstrated in real examples from the Sorbinil Retinopathy Trial, and the Age-Related Macular Degeneration Study. Raw data from these two trials are provided.

Quantitative and qualitative characterization of retinal dystrophies in canine models of inherited retinal diseases using spectral domain optical coherence tomography (SD-OCT).

The purpose of this study was to establish spectral domain optical coherence tomography (SD-OCT) assessment data in well-established canine models of inherited retinal dystrophies: PDE6B-rod-cone dysplasia 1 (RCD1: early onset retinitis pigmentosa), PRCD-progressive rod-cone degeneration (PRCD: late onset retinitis pigmentosa), CNGB3-achromatopsia, and RPE65-Leber congenital amaurosis (LCA). High resolution SD-OCT images of the retina were acquired from both eyes in 5 planes: temporal; superotemporal; superior; nasal; and inferior in adult dogs with: RCD1 (n = 4 dogs, median age: 1.5 yrs); PRCD (n = 2, 4.3 yrs); LCA (n = 3, 5.2 yrs); achromatopsia (n = 3, 4.2 yrs); and wild types (wt, n = 6, 5.5 yrs). Total, inner and outer retinal thicknesses and ellipsoid zone were analyzed. In selected animals, histomorphometric evaluations were performed. In dogs with RCD1, PRCD, and LCA, the thickness of the outer retina was, compared to wt, significantly decreased (p ≤ 0.02) in all OCT imaging planes, and in superotemporal and inferior imaging planes in dogs with achromatopsia. No significant thinning was observed in inner retina thickness in any disease model except in the inferior imaging plane in dogs with RCD1. Dogs with RCD1, PRCD, and LCA had significantly more areas with disrupted ellipsoid zone in the presumed area centralis than wt (p ≤ 0.001). OCT findings provide baseline information for research of retinal dystrophies using these canine models.

Extending Hui-Walter framework to correlated outcomes with application to diagnosis tests of an eye disease among premature infants.

Diagnostic accuracy, a measure of diagnostic tests for correctly identifying patients with or without a target disease, plays an important role in evidence-based medicine. Diagnostic accuracy of a new test ideally should be evaluated by comparing to a gold standard; however, in many medical applications it may be invasive, costly, or even unethical to obtain a gold standard for particular diseases. When the accuracy of a new candidate test under evaluation is assessed by comparison to an imperfect reference test, bias is expected to occur and result in either overestimates or underestimates of its true accuracy. In addition, diagnostic test studies often involve repeated measurements of the same patient, such as the paired eyes or multiple teeth, and generally lead to correlated and clustered data. Using the conventional statistical methods to estimate diagnostic accuracy can be biased by ignoring the within-cluster correlations. Despite numerous statistical approaches have been proposed to tackle this problem, the methodology to deal with correlated and clustered data in the absence of a gold standard is limited. In this article, we propose a method based on the composite likelihood function to derive simple and intuitive closed-form solutions for estimates of diagnostic accuracy, in terms of sensitivity and specificity. Through simulation studies, we illustrate the relative advantages of the proposed method over the existing methods that simply treat an imperfect reference test as a gold standard in correlated and clustered data. Compared with the existing methods, the proposed method can reduce not only substantial bias, but also the computational burden. Moreover, to demonstrate the utility of this approach, we apply the proposed method to the study of National-Eye-Institute-funded Telemedicine Approaches to Evaluating of Acute-Phase Retinopathy of Prematurity (e-ROP), for estimating accuracies of both the ophthalmologist examination and the image evaluation.

Detection of Significant Hyperopia in Preschool Children Using Two Automated Vision Screeners.

SIGNIFICANCE: Moderate to high uncorrected hyperopia in preschool children is associated with amblyopia, strabismus, reduced visual function, and reduced literacy. Detecting significant hyperopia during screening is important to allow children to be followed for development of amblyopia or strabismus and implementation of any needed ophthalmic or educational interventions. PURPOSE: This study aimed to compare the sensitivity and specificity of two automated screening devices to identify preschool children with moderate to high hyperopia. METHODS: Children in the Vision in Preschoolers (VIP) study were screened with the Retinomax Autorefractor (Nikon, Inc., Melville, NY) and Plusoptix Power Refractor II (Plusoptix, Nuremberg, Germany) and examined by masked eye care professionals to detect the targeted conditions of amblyopia, strabismus, or significant refractive error, and reduced visual acuity. Significant hyperopia (American Association for Pediatric Ophthalmology and Strabismus definition of hyperopia as an amblyopia risk factor), based on cycloplegic retinoscopy, was >4.00 D for age 36 to 48 months and >3.50 D for age older than 48 months. Referral criteria from VIP for each device and from a distributor (PediaVision) for the Power Refractor II were applied to screening results. RESULTS: Among 1430 children, 132 children had significant hyperopia in at least one eye. Using the VIP referral criteria, sensitivities for significant hyperopia were 80.3% for the Retinomax and 69.7% for the Power Refractor II (difference, 10.6%; 95% confidence interval, 7.0 to 20.5%; P = .04); specificities relative to any targeted condition were 89.9 and 89.1%, respectively. Using the PediaVision referral criteria for the Power Refractor, sensitivity for significant hyperopia was 84.9%; however, specificity relative to any targeted condition was 78.3%, 11.6% lower than the specificity for the Retinomax. Analyses using the VIP definition of significant hyperopia yielded results similar to when the American Association for Pediatric Ophthalmology and Strabismus definition was used. DISCUSSION: When implementing vision screening programs for preschool children, the potential for automated devices that use eccentric photorefraction to either miss detecting significant hyperopia or increase false-positive referrals must be taken into consideration.

Effect of Omega-3 on HLA-DR Expression by Conjunctival Cells and Tear Cytokine Concentrations in the Dry Eye Assessment and Management Study.

OBJECTIVES: To determine effect of omega-3 supplementation on conjunctival cell HLA-DR expression and tear concentrations of interleukin (IL)-1ß, IL-6, IL-8, IL-10, IL-17A, interferon-γ, and tumor necrosis factor-α in dry eye disease patients in the Dry Eye Assessment and Management study. METHODS: Patients were randomized to receive a daily dose of eicosapentaenoic and docosahexaenoic acids (ω3) or refined olive oil (placebo) for 12 months. At baseline, 6 and 12 months, HLA-DR expression in conjunctival total, epithelial, and white blood cells and cytokine concentration in tears were determined. Differences in change from baseline between treatment groups were assessed using generalized estimating equations (HLA-DR) or Wilcoxon rank-sum test (cytokines). RESULTS: No differences were observed in HLA-DR expression in total, epithelial, or white blood cells between ω3 and placebo groups at 6 months (n=435) or 12 months (n=436). The median concentration percent change differed between ω3 and placebo groups at 6 months for IL-6 (-36.6 vs. 24.5%, P =0.02, n=75) and for IL-8 (3.7% vs. 72.6%, P =0.02, n=68); at 12 months, they did not differ ( P ≥0.18). No other differences between the treatment groups were detected. CONCLUSIONS: ω3 supplementation did not consistently affect ocular inflammatory status as measured by the frequency of HLA-DR expressing conjunctival cells or tear cytokines.

Primary Monocanalicular Stent Intubation for Children With Congenital Nasolacrimal Duct Obstruction: Surgical Outcome and Risk Factors.

PURPOSE: To determine the risk factors impacting the surgical success of primary monocanalicular stent intubation for congenital nasolacrimal duct obstruction (CNLDO). METHODS: This is a retrospective interventional case series of patients 18 years and younger treated more than a 12-year period with monocanalicular stent intubation with inferior turbinate fracture for CNLDO by a single surgeon. Patients with dacryocystoceles, dacryocystitis, Down syndrome and previous tear duct surgery were excluded. An intraoperative grading scale of tear duct stenosis, date of stent removal, stent length, and postoperative symptoms were recorded. Surgical success was defined as the complete resolution of symptoms. RESULTS: One thousand four hundred sixty-nine stents were placed in 1,001 pediatric participants (533 unilateral, 468 bilateral). The mean age at surgery was 1.86 years (0.1-18.07). The mean follow up was 34.99 months (0.43-134.3) with mean in-office stent removal at 3.41 months (0.63-36.9). Early stent loss occurred in 14.8% intubations (217/1,469). The overall success rate was 92.4% (1,357/1,469 eyes). Subjects less than the age of 4 years had a success rate of 92.8% (1,296/1,397) compared with 84.7% (61/72) in children more than 4. In multivariable analysis, bilateral surgery, severe tear duct stenosis, and early stent loss were significantly associated with higher risk of surgical failure. CONCLUSIONS: Severe tear duct stenosis, early stent loss, and bilateral surgery were significant risk factors for surgical failure. While the success rate stratified by age at surgery suggested a lower success after the age of 4. Primary monocanalicular stent intubation is an effective and safe treatment for CNLDO sparing a child the need for multiple staged surgeries.

Preliminary Screening Questionnaire for Sjögren's Syndrome in the Rheumatology Setting.

OBJECTIVE: Sjögren's syndrome (SS) is frequently undetected or misdiagnosed as other rheumatologic diseases. We aimed to develop an SS screening questionnaire for the rheumatology practice. METHODS: We developed the Sjögren's Syndrome Screening Questionnaire (SSSQ) via secondary analysis of data from 974 participants referred by rheumatologists to the Sjögren's International Collaborative Clinical Alliance (SICCA) study. Participants answered 88 questions regarding symptoms, medical history, and demographics. They underwent ocular, dental, and serologic tests and were classified as SS or non-SS using the 2016 American College of Rheumatology/European League Against Rheumatism classification criteria. We conducted univariate and multivariate logistic regression to identify questions most discriminative of SS, from which we derived an individual's likelihood of SS ("SSSQ score"). RESULTS: Five questions were significantly discriminative of SS in the multivariate analysis (p < 0.05): (1) Can you eat a cracker without drinking a fluid/liquid? (no: odds ratio [OR], 1.39; 95% confidence interval [CI], 1.06-1.82]); (2) How would you describe your dental and oral health in general? (fair/poor: OR, 1.68; 95% CI, 1.04-2.75); (3) During the last week, have you experienced tearing? (none of the time: OR, 2.26; 95% CI, 1.23-4.34); (4) Are you able to produce tears? (no: OR, 1.62; 95% CI, 1.12-2.37); and (5) Do you currently smoke cigarettes? (no: OR, 2.83; 95% CI, 1.69-4.91). SSSQ score ≥7 (possible range, 0-11) distinguishes SS from non-SS patients with 64% sensitivity and 58% specificity (area under receiver operating characteristic curve, 0.65). CONCLUSIONS: The SSSQ is a simple 5-item questionnaire designed to screen for SS in clinical practice, with a potential impact to reduce delays in diagnosis.

n-3 Fatty Acid Supplementation for the Treatment of Dry Eye Disease.

BACKGROUND: Dry eye disease is a common chronic condition that is characterized by ocular discomfort and visual disturbances that decrease quality of life. Many clinicians recommend the use of supplements of n-3 fatty acids (often called omega-3 fatty acids) to relieve symptoms. METHODS: In a multicenter, double-blind clinical trial, we randomly assigned patients with moderate-to-severe dry eye disease to receive a daily oral dose of 3000 mg of fish-derived n-3 eicosapentaenoic and docosahexaenoic acids (active supplement group) or an olive oil placebo (placebo group). The primary outcome was the mean change from baseline in the score on the Ocular Surface Disease Index (OSDI; scores range from 0 to 100, with higher scores indicating greater symptom severity), which was based on the mean of scores obtained at 6 and 12 months. Secondary outcomes included mean changes per eye in the conjunctival staining score (ranging from 0 to 6) and the corneal staining score (ranging from 0 to 15), with higher scores indicating more severe damage to the ocular surface, as well as mean changes in the tear break-up time (seconds between a blink and gaps in the tear film) and the result on Schirmer's test (length of wetting of paper strips placed on the lower eyelid), with lower values indicating more severe signs. RESULTS: A total of 349 patients were assigned to the active supplement group and 186 to the placebo group; the primary analysis included 329 and 170 patients, respectively. The mean change in the OSDI score was not significantly different between the active supplement group and the placebo group (-13.9 points and -12.5 points, respectively; mean difference in change after imputation of missing data, -1.9 points; 95% confidence interval [CI], -5.0 to 1.1; P=0.21). This result was consistent across prespecified subgroups. There were no significant differences between the active supplement group and the placebo group in mean changes from baseline in the conjunctival staining score (mean difference in change, 0.0 points; 95% CI, -0.2 to 0.1), corneal staining score (0.1 point; 95% CI, -0.2 to 0.4), tear break-up time (0.2 seconds; 95% CI, -0.1 to 0.5), and result on Schirmer's test (0.0 mm; 95% CI, -0.8 to 0.9). At 12 months, the rate of adherence to treatment in the active supplement group was 85.2%, according to the level of n-3 fatty acids in red cells. Rates of adverse events were similar in the two trial groups. CONCLUSIONS: Among patients with dry eye disease, those who were randomly assigned to receive supplements containing 3000 mg of n-3 fatty acids for 12 months did not have significantly better outcomes than those who were assigned to receive placebo. (Funded by the National Eye Institute, National Institutes of Health; DREAM ClinicalTrials.gov number, NCT02128763 .).

Systemic Conditions Associated with Severity of Dry Eye Signs and Symptoms in the Dry Eye Assessment and Management Study.

PURPOSE: Certain systemic conditions are reported to be risk factors for dry eye disease (DED), but their associations with DED severity are not well studied. We evaluated whether systemic conditions reported to be DED risk factors are associated with severity of DED signs and symptoms. DESIGN: Secondary analysis of data from the Dry Eye Assessment and Management Study, a large-scale multicenter randomized clinical trial of patients with moderate to severe DED. PARTICIPANTS: Five hundred thirty-five adult patients with moderate to severe DED from 27 United States centers. METHODS: Patients reported their medical history at baseline. They underwent ocular surface examinations and symptom evaluation using standardized protocols at baseline, 6 months, and 12 months. We analyzed the associations of systemic conditions (a systemic disease or smoking history) reported as potential DED risk factors with the severity of DED signs and symptoms using generalized linear regression models adjusted by age, gender, race, and visit. MAIN OUTCOME MEASURES: Dry eye disease symptoms assessed using the Ocular Surface Disease Index (OSDI), 6 DED signs (tear film break-up time, anesthetized Schirmer testing, corneal fluorescein staining, conjunctival lissamine green staining, tear osmolarity, and meibomian gland dysfunction), and a composite signs severity score from 0 to 1 (1 = most severe). RESULTS: The mean age was 58 years; 81% were women. More severe DED signs were associated significantly with Sjögren syndrome (mean composite signs severity score 0.52 with disease vs. 0.43 without disease; P < 0.001), facial rosacea (0.47 vs. 0.43; P = 0.002), rheumatoid arthritis (0.47 vs. 0.42; P = 0.002), peripheral artery disease (0.50 vs. 0.43; P < 0.001), and daily smoking history (0.45 vs. 0.43; P = 0.047). Thyroid dysfunction, osteoarthritis, diabetes, irritable bowel syndrome, hypercholesterolemia, hypertension, and hypertriglyceridemia were not associated significantly with DED signs. No conditions were associated significantly with OSDI. CONCLUSIONS: In this large, well-characterized cohort of patients with DED assessed under standardized procedures, patients with certain systemic diseases and smoking history showed more severe DED signs compared with patients without the conditions. The profile of significant DED signs varied by systemic condition, reflecting different DED causes. Understanding the systemic conditions and underlying causes that predispose some patients to severe DED can improve management.

Retinal Detachment after Treatment of Retinopathy of Prematurity with Laser versus Intravitreal Anti-Vascular Endothelial Growth Factor.

PURPOSE: To compare rates of short-term retinal detachment (RD) of infants treated for type 1 retinopathy of prematurity (ROP) with intravitreal anti-vascular endothelial growth factor (VEGF) therapy with infants treated with laser therapy. The choice between these 2 treatments remains controversial. Comparative data are limited and describe re-treatment rates rather than retinal structural outcomes predictive of long-term vision. Anti-vascular endothelial growth factor acts faster than laser therapy, which may be beneficial for more aggressive ROP. DESIGN: Nonrandomized, comparative cohort study. PARTICIPANTS: The study included 1167 eyes of 640 infants treated for type 1 ROP. Among these, 164 eyes received anti-VEGF therapy and 1003 eyes received laser therapy. METHODS: Pretreatment and posttreatment examinations and treatments were completed by ophthalmologists with expertise in ROP. The study was a secondary analysis of data from the retrospective Postnatal Growth and Retinopathy of Prematurity Study (G-ROP) 1 study (2006-2012) and the prospective G-ROP 2 study (2015-2017). MAIN OUTCOME MEASURES: Rate of RD (ROP stages 4A, 4B, or 5) within 8 weeks of initial treatment, an end point predictive of poor long-term vision. The results were stratified by postmenstrual age (PMA) at treatment as occurring before versus at or after 36 weeks and 0 days, because earlier disease may be considered more aggressive. RESULTS: Among 458 eyes treated before PMA 36 weeks and 0 days, the short-term RD rate was higher after laser therapy (29/368 eyes [7.9%]) than after anti-VEGF therapy (0/90 eyes [0%]; P < 0.001). Of 709 eyes treated at or after PMA 36 weeks and 0 days, short-term RD risk did not differ between groups (laser [20/635 eyes], 3.1%; anti-VEGF [1/74 eyes], 1.4%; P = 0.27). CONCLUSIONS: Anti-vascular endothelial growth factor therapy results in better short-term structural outcomes than laser therapy when type 1 ROP is treated before 36 weeks' PMA. After this age, both treatments have very low rates of short-term RD. The faster action of anti-VEGF agents likely is responsible for these findings.

Changes in Intraocular Pressure and Angle Structure after Dilation in Primary Angle-Closure Suspects with Visually Significant Cataract.

PURPOSE: To evaluate the safety of pupillary dilation in primary angle-closure suspects (PACS) with concurrent visually significant cataract (VSC), to identify risk factors associated with elevated intraocular pressure (IOP), and to describe changes in anterior segment anatomy after pupillary dilation. DESIGN: Prospective study. PARTICIPANTS: Patients with PACS and VSC and no prior laser or intraocular surgery were recruited. Visually significant cataract was defined as best-corrected visual acuity ≤ 20/40 due to cataract. METHODS: Subjects' eyes were dilated with 0.5% tropicamide and 0.5% phenylephrine hydrochloride. A standardized eye examination, biometry, and swept-source OCT (SS-OCT) were performed before dilation. Intraocular pressure and SS-OCT were repeated 1, 4, and 6 hours postdilation (PDH1, PDH4, and PDH6, respectively). All parameters were compared between time points before and after dilation using paired t test. Linear regression models were used to determine the risk factors associated with postdilation IOP changes. MAIN OUTCOME MEASURES: Change in IOP and SS-OCT parameters from baseline. RESULTS: Seventy-eight eyes from 78 patients were included, with 78, 66, and 12 patients completing the study at PDH1, PDH4, and PDH6, respectively. Mean IOP increased from 14.8 ± 2.6 mmHg at baseline to 15.5 ± 3.5 mmHg at PDH1 (P = 0.03) and decreased to 14.9 ± 3.1 mmHg at PDH4 (P = 0.09). Four patients (5.13%) and 3 patients (3.85%) had an increase in IOP ≥ 5 mmHg at PDH1 and PDH4, respectively. Two patients (2.56%) and 1 patient (1.28%) had an increase in IOP ≥ 8 mmHg at PDH1 and PDH4, respectively. None developed acute primary angle-closure during the observation period. Almost all anterior chamber parameters showed a significant increase after dilation at PDH1 and PDH4, except lens vault and iris volume, which decreased at PDH1 and PDH4 from baseline. Increase in anterior chamber depth was negatively associated with the level of IOP elevation after dilation (P < 0.01). CONCLUSIONS: Dilation of patients' eyes with PACS and VSC in this cohort appears to have a low risk for IOP spike. This may be associated with relaxation of the ciliary muscle leading to posterior displacement of the lens-iris diaphragm and deepening of the anterior chamber.

The Effect of Tube Location on Corneal Endothelial Cells in Patients with Ahmed Glaucoma Valve.

PURPOSE: To compare the effects of the Ahmed glaucoma valve (AGV; New World Medical, Rancho Cucamonga, CA) with sulcus versus anterior chamber (AC) tube placement on the corneal endothelial density and morphology over time. DESIGN: Nonrandomized, interventional study. PARTICIPANTS: This study included 106 eyes from 101 pseudophakic patients who had the AGV tube placed in the AC (acAGV) and 105 eyes from 94 pseudophakic patients who had the AGV tube placed in the ciliary sulcus (sAGV). METHODS: All patients underwent preoperative specular microscopy, which was repeated postoperatively in 2019. The patients' demographic information, glaucoma diagnoses, and basic ocular information were obtained on chart review. Anterior segment OCT was conducted for patients who underwent sAGV to evaluate the sulcus tube position. Gonioscopy was performed to document peripheral anterior synechiae (PAS). Linear mixed-effects models were used to compare the different ocular and endothelial measurements between the 2 groups and to identify risk factors for endothelial cell density (ECD) loss over time. MAIN OUTCOME MEASURES: Monthly change in corneal endothelial measurements, including ECD and coefficient of variation (CV), calculated as the difference between preoperative and postoperative measurements divided by the number of months from the time of surgery to postoperative specular microscopy. RESULTS: The acAGV and sAGV groups were comparable in all baseline characteristics except that the acAGV group had longer follow-up (37.6 vs. 20.1 months, respectively, P < 0.001). Mean monthly loss in central ECD was significantly more in the acAGV group (mean ± standard deviation: 29.3±29.7 cells/mm2) than in the sAGV group (15.3±20.7 cells/mm2, P < 0.0001). Mean monthly change in CV was similar between the 2 groups (P = 0.28). Multivariate analyses revealed that younger age and tube location in the AC were associated with faster central ECD loss (P = 0.02, P < 0.0001, respectively). For patients with sAGV, while PAS was associated with faster central ECD loss (P = 0.002), a more forward tube position tenting the iris was not (P > 0.05). CONCLUSIONS: Compared with anterior segment placement, ciliary sulcus tube implantation may be a preferred surgery approach to reduce endothelial cell loss in pseudophakic patients.