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.

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: One hundred thirty-six patients aged ≤18 years with glaucoma/glaucoma suspect, and least 1 completed 24 to 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 to 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 < .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 < .02), and number of prior VF tests was not (P = .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.

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.

Malignancy Risk Associated with the Use of Systemic Immunomodulatory Therapy in the Management of Non-infectious Uveitis.

PURPOSE: Patients with non-infectious uveitis (NIU) can require treatment with systemic immunomodulatory therapy (IMT), but it is unclear whether IMT drug categories increase the risk of malignancy in NIU patients. The purpose of this study is to determine if the use of systemic IMT in patients with NIU is associated with an increased risk of malignancy. DESIGN: Clinical cohort study METHODS: Patients were identified from a U.S. administrative medical claims database including some Medicare Advantage and commercial plans, from 2000 to 2022. 318,499 NIU patients were identified. Enrollees were included in the analysis if they met the following criteria: continuous enrollment in the plan for at least 1 year, and at least two consecutive visit diagnoses of any type of NIU, after initiation of systemic IMT. We compared the rates of incident malignancy in NIU patients treated with IMT versus the rates among NIU patients not treated with IMT. Multivariable Cox regression models were used to predict the hazard of developing incident cancer. RESULTS: Of the 318,498 patients with NIU identified over a 15-year period, 318,996 did not develop malignancy, and 492 did develop malignancy. Of the patients that developed a malignancy, 280 (57%) were treated with systemic corticosteroids; 204 (41%) were treated with antimetabolites; 44 (9%) were treated with T cell inhibitors; 108 (22%) were treated with TNF alpha inhibitors; 2 (0.004%) were treated with interleukin -6 (IL-6) inhibitors; and 1 was treated with CD-20 antibodies. There were no malignancies reported in the group treated with alkylating agents. There was no association between any of the drug classes and incidence of malignancy. CONCLUSION: This study suggests that there is no increased risk of malignancy associated with the use of systemic IMT for patients with NIU.

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.

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.

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.

The association of stroke with herpes zoster ophthalmicus.

BACKGROUND/OBJECTIVES: Studies have reported an association between herpes zoster ophthalmicus (HZO) and stroke. We sought to validate this association with rigorous controls for both medical comorbidities and social factors using a nationwide U.S. administrative medical claims database. SUBJECTS/METHODS: A two-step approach was taken: first a retrospective case-control study was performed, followed by a self-controlled case series (SCCS). For the case control study, cox proportional hazard regression with inverse proportional treatment weighting assessed the hazard for stroke. In the SCCS, incidence of stroke was compared prior to and after the diagnosis of HZO. RESULTS: For the case-control study, 25,720 cases and 75,924 controls met our eligibility criteria. 1712 (6.7%) and 4544 (6.0%) strokes occurred in the case and control groups respectively, conferring an 18% increased risk of stroke in the observed 1-year post-HZO period (HR = 1.18, 95% CI: 1.12-1.25, p < 0.001). SCCS analysis showed the risk for stroke was highest in the month immediately after HZO episode compared to any other time range (1-30 days after, relative risk 1.58, p < 0.001) and even higher when assessing time more distal time points prior to the HZO diagnosis (days 1-30 after HZO diagnosis had RR = 1.69 (95% CI: 1.38-2.07) and RR = 1.93 (95% CI: 1.55-2.39) compared with days -120 to -91 and -150 to -121 prior to index, respectively (p < 0.001). CONCLUSIONS: After accounting for stroke risk factors, our analysis confirms the association between HZO and stroke, with highest risk in the immediate month after an episode.

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.

Visit Adherence and Visual Acuity in Study of COmparative Treatments for REtinal Vein Occlusion 2 (SCORE2).

PURPOSE: We quantify the association between visit adherence and visual acuity (VA) in retinal vein occlusions (CRVO). METHODS: The SCORE2 protocol included a visit every 4 weeks (every 28-35 days) during the first year. Visit adherence was measured as follows: number of missed visits, average and longest (avg and max days) visit interval, and average and longest (avg and max missed days) and unintended visit interval. Avg and max missed days were categorized as on time (0 days), late (>0-60 days), and very late (>60 days). The primary outcome was a change in the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity letter score (VALS) between baseline study visit and last attended visit during Year 1, using multivariate linear regression models controlling for numerous demographic and clinical factors. RESULTS: After adjustment, for each visit missed, patients lost 3.0 letters (95% CI: -6.2, 0.2) of vision (p = .07). On average, the 48 patients who missed at least 1 visit lost 9.4 letters (95% CI: -14.4, -4.3, p < .001) of vision after adjustment. Average days and maximal intervals between visits were not associated with changes in VALS (p > .22) for both comparisons. However, when a visit was missed, the average missed days between missed visits and the max missed interval were both associated with loss of VALS (both variables: 0 days missed as reference, late [1-60 days] -10.8 letters [95% CI: -16.9, -4.7], very late [>60 days] -7.3 letters [95% CI: -14.5, -0.2]; p = .003 for both). CONCLUSIONS: Visit adherence is associated with VALS outcomes in CRVO patients.

Real-world socioeconomic determinants of corneal crosslinking in a national cohort.

PURPOSE: To characterize recent socioeconomic trends in patients with keratoconus/corneal ectasias undergoing corneal crosslinking (CXL). SETTING: A deidentified administrative medical claims database comprised commercial and Medicare Advantage health claims from across the United States. DESIGN: Population-based retrospective cohort study. METHODS: This study identified 552 patients with keratoconus/corneal ectasia who underwent CXL and 2723 matched controls who did not undergo CXL based on Current Procedural Terminology coding from a U.S. national insurance claims database from 2016 to 2020. For each patient, characteristics, including sex, race, age, household net worth, education level, insurance plan type, and geographic region, were extracted. Multivariate logistic regression was conducted to determine the odds of undergoing crosslinking. RESULTS: Age 30 years or older (odds ratio [OR], 0.34, P < .001) was associated with decreased likelihood of undergoing CXL. Sex, race, education, and patient income were not associated with odds of undergoing CXL. Patients with health maintenance organization insurance had lower odds of undergoing CXL (OR, 0.64, P = .047). Geographically, patients on the east coast (OR, 0.37, P < .001) and Lower Midwest (OR, 0.31, P < .001) had statistically lower odds of undergoing crosslinking. CONCLUSIONS: This is the first study to identify socioeconomic determinants of CXL, and it highlights that geographic location and insurance type may limit accessibility to patients.

SGLT2 inhibitors and diabetic retinopathy progression.

PURPOSE: To evaluate whether sodium-glucose co-transporter 2 (SGLT2) inhibitors affect progression of non-proliferative diabetic retinopathy (NPDR) compared to standard of care. METHODS: A retrospective cohort study compared subjects enrolled in a commercial and Medicare Advantage medical claims database who filled a prescription for a SGLT2 inhibitor between 2013 and 2020 to unexposed controls, matched up to a 1:3 ratio. Patients were excluded if they were enrolled for less than 2 years in the plan, had no prior ophthalmologic exam, had no diagnosis of NPDR, had a diagnosis of diabetic macular edema (DME) or proliferative diabetic retinopathy (PDR), had received treatment for vision-threatening diabetic retinopathy (VTDR), or were younger than 18 years. To balance covariates of interest between the cohorts, an inverse probability treatment weighting (IPTW) propensity score for SGLT2 inhibitor exposure was used. Multivariate Cox proportional hazard regression modeling was employed to assess the hazard ratio (HR) for VTDR, PDR, or DME relative to SGLT2 exposure. RESULTS: A total of 6065 patients who initiated an SGLT2 inhibitor were matched to 12,890 controls. There were 734 (12%), 657 (10.8%), and 72 (1.18%) cases of VTDR, DME, and PDR, respectively, in the SGLT2 inhibitor cohort. Conversely, there were 1479 (11.4%), 1331 (10.3%), and 128 (0.99%) cases of VTDR, DME, and PDR, respectively, among controls. After IPTW, Cox regression analysis showed no difference in hazard for VTDR, PDR, or DME in the SGLT2 inhibitor-exposed cohort relative to the unexposed group [HR = 1.04, 95% CI 0.94 to 1.15 for VTDR; HR = 1.03, 95% CI 0.93 to 1.14 for DME; HR = 1.22, 95% CI 0.89 to 1.67 for PDR]. CONCLUSION: Exposure to SGLT2 inhibitor therapy was not associated with progression of NPDR compared to patients receiving other diabetic therapies.

Association of Ocular Surface Immune Cells With Dry Eye Signs and Symptoms in the Dry Eye Assessment and Management (DREAM) Study.

Purpose: Dry eye disease (DED) is a multifactorial, heterogeneous disease of the ocular surface with one etiology being ocular surface inflammation. Studies using animal models demonstrate the role of ocular surface immune cells in the inflammatory pathway leading to DED, but few have evaluated humans. This study described the white blood cell population from the ocular surface of patients with DED and assessed its association with DED signs and symptoms in participants of the Dry Eye Assessment and Management (DREAM) study. Methods: Participants were assessed for symptoms using the Ocular Surface Disease Index, signs via corneal staining, conjunctival staining, tear break-up time, and Schirmer test, and Sjögren's syndrome (SS) based on the 2012 American College of Rheumatology classification criteria. Impression cytology of conjunctival cells from each eye was evaluated using flow cytometry: T cells, helper T cells (Th), regulatory T cells (Tregs), cytotoxic T cells, and dendritic cells. Results: We assessed 1049 eyes from 527 participants. White blood cell subtype percentages varied widely across participants. Significant positive associations were found for Th and conjunctival staining (mean score of 2.8 for 0% Th and 3.1 for >4.0% Th; P = 0.007), and corneal staining (mean score of 3.5 for 0% Th and 4.3 for >4.0% Th; P = 0.01). SS was associated with higher percent of Tregs (median 0.1 vs. 0.0; P = 0.01). Conclusions: Th were associated with more severe conjunctival and corneal staining, possibly indicating their role in inflammation leading to damage of the ocular surface. There is no consistent conclusion about Tregs in SS, but these results support that Tregs are elevated in SS.

Association of Dry Eye Symptoms and Signs in Patients with Dry Eye Disease.

PURPOSE: To determine the correlations among symptoms and signs of dry eye disease (DED) in the Dry Eye Assessment and Management (DREAM) study. METHODS: A total of 535 patients with moderate-to-severe DED were assessed for symptoms using the Ocular Surface Disease Index (OSDI) and four DED signs in both eyes (conjunctival lissamine green staining, corneal fluorescein staining, Schirmer's testing, and tear break-up time (TBUT)) following standardized protocols at baseline and follow-up visits (months 3, 6, and 12). Spearman correlation coefficients (rho) were calculated for correlations among symptoms and signs of DED at baseline and among changes in symptoms and signs from baseline at 12 months. The confidence intervals and p-values for correlation coefficients were calculated using a cluster bootstrapping to account for inter-eye correlation. RESULTS: At baseline, OSDI total score was not correlated with signs; however, OSDI subscale score of ocular symptoms was weakly correlated with corneal staining score (rho = 0.14, p = .002) and Schirmer test score (rho = 0.11, p = .01). There were statistically significant correlations among the four signs (p < .001), with absolute correlation coefficient ranging from 0.14 (conjunctival staining score vs. TBUT) to 0.33 (conjunctival staining score vs. cornea staining score). The correlations among changes in symptoms and signs were weaker, with the highest correlation between change in conjunctival staining and corneal staining (rho = 0.21, p < .001). CONCLUSIONS: Consistent with previous studies, among DREAM participants with moderate-to-severe DED at baseline, correlations of DED symptoms with signs were low and correlations among four objective signs were low to moderate. The correlations among changes in symptoms and signs were even weaker.

Dynamic structural remodeling of the human visual system prompted by bilateral retinal gene therapy.

The impact of changes in visual input on neuronal circuitry is complex and much of our knowledge on human brain plasticity of the visual systems comes from animal studies. Reinstating vision in a group of patients with low vision through retinal gene therapy creates a unique opportunity to dynamically study the underlying process responsible for brain plasticity. Historically, increases in the axonal myelination of the visual pathway has been the biomarker for brain plasticity. Here, we demonstrate that to reach the long-term effects of myelination increase, the human brain may undergo demyelination as part of a plasticity process. The maximum change in dendritic arborization of the primary visual cortex and the neurite density along the geniculostriate tracks occurred at three months (3MO) post intervention, in line with timing for the peak changes in postnatal synaptogenesis within the visual cortex reported in animal studies. The maximum change at 3MO for both the gray and white matter significantly correlated with patients' clinical responses to light stimulations called full field sensitivity threshold (FST). Our results shed a new light on the underlying process of brain plasticity by challenging the concept of increase myelination being the hallmark of brain plasticity and instead reinforcing the idea of signal speed optimization as a dynamic process for brain plasticity.

Microbial patterns and culture utility in orbital cellulitis.

PURPOSE: To determine the prevalence and types of pathogens found in children with orbital cellulitis and to evaluate the utility of nonoperative cultures. METHODS: This was a retrospective cohort study of children with imaging-confirmed orbital cellulitis over a period of 8 years. Outcomes included prevalence and types of organisms, polymicrobial infection, mixed aerobic-anaerobic infection, effect of age, and culture utility. RESULTS: Of 220 children with orbital cellulitis, 112 (51%) had cultures taken; 69 (31%) had surgical intervention. Culture sources for the 112 children with cultures included blood (57 patients [51%]), sinus (53 [47%]), orbit (42 [38%]), brain (6 [5%]), and skin/conjunctiva/lacrimal sac (6 [5%]). Streptococcus anginosus group strains grew in cultures from 19 children (17%); methicillin-sensitive Staphylococcus aureus (MSSA), in 15 (13%); Streptococcus pyogenes, in 12 (11%); methicillin-resistant Staphylococcus aureus (MRSA), in 6 (5%); anaerobic/facultative gram negative rods, in 8 (7%); anaerobic Gram-positive cocci, other Viridans group streptococci, and Streptococci pneumoniae, in 3 (3%) each; and normal respiratory/skin flora, in 23 (21%). Polymicrobial infection (P = 0.08) and anaerobic organisms (P = 0.58) did not differ by age (range, 0.1-16.8 years). In all 220 (100%) children, nonoperative cultures were either not obtained (108 [49%]), not helpful in avoiding surgery (69 [31%]), showed no growth (39 [18%]), or grew an organism that did not change management from empiric therapy (4 [2%]). CONCLUSIONS: While many organisms may be cultured from children with orbital cellulitis, Streptococcus and MSSA were the most common in our study cohort. MRSA is uncommon, so initial empiric coverage is not necessary. Rates of polymicrobial and anaerobic infection were similar across ages. Our results indicate that nonoperative cultures are not indicated in the initial medical management of orbital cellulitis; in our cohort, they neither resulted in treatment changes nor helped avoid surgery.

Erythropoiesis-Stimulating Agents and the Risk of Vision-Threatening Diabetic Retinopathy.

PURPOSE: Animal studies have suggested that Erythropoiesis-Stimulating Agents (ESAs) may increase vascular endothelial growth factor (VEGF)-related retinopathies, but this effect is unclear in humans. This study evaluates the risk of vision-threatening diabetic retinopathy (VTDR), defined as either diabetic macular edema (DME) or proliferative diabetic retinopathy (PDR), in patients exposed to an ESA. METHODS: Two analyses were performed. First, a retrospective matched-cohort study was designed using a de-identified commercial and Medicare Advantage medical claims database. The ESA cohort of non-proliferative diabetic retinopathy patients who were new users of an ESA from 2000 to 2022 was matched to controls up to a 3:1 ratio. Exclusion criteria included less than 2 years in the plan, history of VTDR or history of other retinopathy. Multivariable Cox proportional hazards regression with inverse proportional treatment weighting (IPTW) was used to assess the hazard of developing VTDR, DME, and PDR. The second analysis was a self-controlled case series (SCCS) evaluating the incidence rate ratios (IRR) of VTDR during 30-day periods before and after initiating an ESA. RESULTS: After inclusion of 1502 ESA-exposed patients compared with 2656 controls, IPTW-adjusted hazard ratios found the ESA cohort had an increased hazard of progressing to VTDR (HR = 3.0 95%CI:2.3-3.8;p < .001) and DME (HR = 3.4,95%CI:2.6-4.4,p < .001), but not PDR (HR = 1.0,95%CI:0.5-2.3,p = .95). Similar results were found within the SCCS which demonstrated higher IRRs for VTDR (IRRs = 1.09-1.18;p < .001) and DME (IRRs = 1.16-1.18;p < .001), but not increased IRRs in PDR (IRR = 0.92-0.97,p = .02-0.39). CONCLUSION: ESAs are associated with higher risks for VTDR and DME, but not PDR. Those studying ESAs as adjunctive therapy for DR should be cautious of possible unintended effects.