PURPOSE: To determine the cumulative incidence of retinal detachment (RD) repair following pediatric cataract surgery and identify the associated risk factors. DESIGN: US population-based insurance claims retrospective cohort study. PARTICIPANTS: Patients ≤ 18 years old who underwent cataract surgery in 2 large databases: Optum Clinformatics (2003-2021) and IBM MarketScan (2007-2016). METHODS: Individuals with ≥ 6 months of prior enrollment were included, and those with a history of RD, RD repair, traumatic cataract, spherophakia, or ectopia lentis were excluded. The primary outcome was time between initial cataract surgery and RD repair. The risk factors investigated included age, sex, persistent fetal vasculature (PFV), prematurity, intraocular lens (IOL) placement, and pars plana lensectomy approach. MAIN OUTCOME MEASURES: Kaplan-Meier estimated cumulative incidence of RD repair 5 years after cataract surgery and hazard ratios (HRs) with 95% confidence intervals (CIs) from multivariable Cox proportional hazards regression models. RESULTS: Retinal detachment repair was performed on 47 of 3289 children included in this study. The cumulative incidence of RD repair within 5 years of cataract surgery was 2.0% (95% CI, 1.3%-2.6%). Children requiring RD repair were more likely to have a history of prematurity or PFV and less likely to have an IOL placed (all P < 0.001). Factors associated with RD repair in the multivariable analysis included a history of prematurity (HR, 6.89; 95% CI, 3.26-14.56; P < 0.001), PFV diagnosis (HR, 8.20; 95% CI, 4.11-16.37; P < 0.001), and IOL placement (HR, 0.44; 95% CI, 0.21-0.91; P = 0.03). Age at surgery, sex, and pars plana lensectomy approach were not significantly associated with RD repair after adjusting for all other covariates. CONCLUSIONS: Approximately 2% of patients will undergo RD repair within 5 years of pediatric cataract surgery. Children with a history of PFV and prematurity undergoing cataract surgery without IOL placement are at the greatest risk.

Management of pediatric choroidal hemangioma complicated by large exudative retinal detachment can be challenging, with few options available. Limited data have been published on outcomes following proton radiotherapy (PRT) for management of these patients. In this retrospective case series, nine patients were treated with a low-dose PRT regimen of 20 Gy(relative biological effectiveness [RBE]) in 10 fractions, and two were treated with 15 Gy(RBE) in four fractions. Visual acuity improved in seven patients (64%) and remained stable in the remaining four (36%). In patients with imaging follow-up (10 patients), subretinal fluid resolved in nine patients (90%) and tumor thickness decreased or remained stable in 10 (100%). Complications were observed in eight of 11 patients (73%). One patient developed grade 2 cataract; otherwise, no grade ≥2 complications were observed.

PURPOSE: Published studies of amblyopia include only patients with visual acuity (VA) worse than 20/40 in one or both eyes. This study evaluates patients diagnosed and treated as amblyopic despite not meeting traditional visual acuity criteria for amblyopia. DESIGN: Retrospective clinical cohort study. METHODS:  SETTING: INSTITUTIONAL PRACTICE. PATIENT POPULATION: All patients diagnosed with amblyopia at Boston Children's Hospital between 2010-2014. INCLUSION CRITERIA: VA better than 20/40 but not correctable to 20/20 in one or both eyes; age 2-12 years. OBSERVATIONS: Demographics, VA, baseline characteristics. OUTCOME MEASURES: Resolution, defined as VA 20/20 in both eyes; stereopsis at last follow-up. RESULTS:  Of 2311 patients reviewed, 464 (20.1%) had subthreshold amblyopia. A majority (61.7%) had an amblyogenic factor, most commonly anisometropia (32.8%). Patients were followed for a median of 3.1 years; nearly all (97.5%) were treated. Of 318 patients who returned for follow-up, 47.8% achieved resolution, including 55.7% of treatment-naïve patients and 62.5% (5 of 8 patients) offered observation alone. Median stereopsis improved by 0.4 log units in those who achieved resolution, with no change in those with persistent amblyopia. In the multivariate analysis, a longer length of follow-up was significantly associated with resolution of subthreshold amblyopia (OR 1.38; 95% confidence interval 1.22 to 1.57, p<.001). DISCUSSION: Patients with subthreshold amblyopia represent a sizeable cohort in real-world amblyopia practice. When offered treatment, half achieved 20/20 vision in both eyes with improved stereopsis as well. Further studies are needed to assess whether observation alone would result in similar outcomes.

PURPOSE: To evaluate agreement of nonmydriatic confocal scanning laser ophthalmoscopy (SLO; EIDON [CenterVue]) and the 7-standard field ETDRS area on ultrawide-field (UWF) SLO imaging for identification of diabetic retinopathy (DR) severity. DESIGN: Single-site, prospective, comparative, instrument validation study. PARTICIPANTS: One hundred ten eyes of 55 patients with diabetes mellitus were evaluated. METHODS: Each patient underwent nonmydriatic, nonsimultaneous stereoscopic imaging using the EIDON camera and 4 fields of 60° × 55° were acquired (macula centered, disc centered, temporal macula, superotemporal). Mydriatic UWF retinal images were acquired using a nonsimultaneous stereographic protocol with UWF imaging (California; Optos plc). Before grading, a standardized ETDRS 7-field image mask was applied to all UWF retinal images. Images from each device were graded independently by 2 masked graders using the ETDRS clinical DR classification. Any discrepancy in DR grading between the devices was adjudicated by a third grader. MAIN OUTCOME MEASURES: κ Levels of agreement, sensitivity, and specificity for DR thresholds. RESULTS: Severity by ETDRS grading was as follows: no DR, 10.9%; mild nonproliferative DR (NPDR), 45.5%; moderate NPDR, 16.5%; severe NPDR, 11.8%; proliferative DR, 12.7%; high-risk proliferative DR, 2.7%; and ungradable, 0%. After adjudication, the level of DR identified on EIDON images agreed exactly with that of UWF ETDRS imaging in 87% of eyes (n = 96) and was within 1 step in 99.1% of eyes (n = 109) with a simple κ value of 0.8244 ± 0.0439 (95% confidence interval [CI], 0.7385-0.9104) and weighted (linear) κ value of 0.9041 ± 0.0257 (95% CI, 0.8537-0.9545). Sensitivity and specificity compared with ETDRS field grading for any DR were 0.96 and 0.75, for moderate NPDR or worse were 0.96 and 0.97, and for severe NPDR or worse were 0.91 and 1.00, respectively. CONCLUSIONS: Nonmydriatic 4-field stereoscopic widefield imaging using the EIDON device was comparable with the DR severity identified within the ETDRS 7-standard field area of UWF images. Future studies will need to evaluate the applicability of this device as a clinical and research tool and the impact of different widefield coverage areas.

Ultraviolet light A (UVA) is the only UV light that reaches the retina and can cause indirect damage to DNA via absorption of photons by non-DNA chromophores. Previous studies demonstrate that UVA generates reactive oxygen species (ROS) and leads to programmed cell death. Programmed cell death (PCD) has been implicated in numerous ophthalmologic diseases. Here, we investigated receptor interacting protein 1 and 3 (RIPK1 and RIPK3) kinases, key signaling molecules of PCD, in UVA-induced photoreceptor injury using in vitro and ex vivo models. UVA irradiation activated RIPK3 but not RIPK1 and mediated necroptosis through MLKL that lie downstream of RIPK3 and induced apoptosis through increased oxidative stress. Moreover, RIPK3 but not RIPK1 inhibition suppresses UVA-induced cell death along with the downregulation of MLKL and attenuates the levels of oxidative stress and DNA fragmentation. In conclusion, these results identify RIPK3, not RIPK1, as a critical regulator of UVA-induced necroptosis cell death in photoreceptors and highlight RIPK3 potential as a neuroprotective target.

BACKGROUND: Cerebral visual impairment (CVI) is a brain based visual disorder associated with the maldevelopment of central visual pathways. Individuals with CVI often report difficulties finding a target of interest in cluttered and crowded visual scenes. However, it remains unknown how manipulating task demands and other environmental factors influence visual search performance in this population. AIM: We developed a novel and naturalistic virtual reality (VR) based static visual search task combined with eye tracking called the "virtual toy box" to objectively assess visual search performance in CVI. METHODS AND PROCEDURES: A total of 38 individuals with CVI (mean age 13.18 years ± 3.58 SD) and 53 controls with neurotypical development (mean age 15.25 years ± 5.72 SD) participated in the study. In a first experiment, study subjects were instructed to search for a preselected toy presented among a varying number of surrounding distractor toys (set size ranging from 1 to 36 items). In a second experiment, we assessed the effects of manipulating item spacing and the size of the visual area explored (field of view; FOV). OUTCOMES AND RESULTS: Behavioral outcomes collected were success rate, reaction time, gaze error, visual search area, and off-screen percent (an index of task compliance). Compared to age-matched controls, participants with CVI showed an overall impairment with respect to all the visual search outcomes of interest. Specifically, individuals with CVI were less likely and took longer to find the target, and search patterns were less accurate and precise compared to controls. Visual search response profiles were also comparatively less efficient and were associated with a slower initial pre-search (visual orienting) response as indexed by higher slope and intercept values derived from the analysis of reaction time × set size functions. Search performance was also more negatively affected in CVI at the smallest as well as largest spacing conditions tested, while increasing FOV was associated with greater decreased gaze accuracy and precision CONCLUSIONS AND IMPLICATIONS: These results are consistent with a general profile of impaired visual search abilities in CVI as well as worsening performance with increased visual task demands and an overall sensitivity to visual clutter and crowding. The observed profile of impaired visual search performance may be associated with dysfunctions related to how visual selective attention is deployed in individuals with CVI.

OBJECTIVE: Gene therapy is a promising approach in the treatment of cardiovascular diseases. Preclinical and clinical studies have demonstrated that adeno-associated viral vectors are the most attractive vehicles for gene transfer. However, preexisting immunity, delayed gene expression, and postinfection immune response limit the success of this technology. The aim of this study was to investigate the efficacy of the first synthetic adeno-associated viral lineage clone, Anc80L65, for cardiac gene therapy. METHODS: By combining 2 different reporter approaches by fluorescence with green fluorescent protein and bioluminescence (Firefly luciferase), we compared transduction efficiency of Anc80L65 and adeno-associated virus, serotype 9 in neonatal rat cardiomyocytes ex vivo and rat hearts in vivo after intramyocardial and intracoronary administration. RESULTS: In cardiomyocytes, Anc80L65 provided a green fluorescent protein expression of 28.9% (36.4 ± 3.34 cells/field) at 24 hours and approximately 100% on day 7. In contrast, adeno-associated virus, serotype 9 green fluorescent protein provided minimal green fluorescent protein expression of 5.64% at 24 hours and 11.8% on day 7. After intramyocardial injection, vector expression peaked on day 7 with Anc80L65; however, with adeno-associated virus, serotype 9 the peak expression was during week 6. Administration of Anc80L65 demonstrated significantly more efficient expression of reporter gene than after adeno-associated virus, serotype 9 at 6 weeks (6.81 ± 0.64 log10 gc/100 ng DNA vs 6.49 ± 0.28 log10 gc/100 ng DNA, P < .05). These results were consistent with the amount of genome copy per cell observed in the heart. CONCLUSIONS: Anc80L65 vector allows fast and robust gene transduction compared with adeno-associated virus, serotype 9 vector in cardiac gene therapy. Anc80L65 did not adversely affect cardiac function and caused no inflammatory response or toxicity.

Aging causes an irreversible, cumulative decline in neuronal function. Using the visual system as a model, we show that astrocytes play a critical role in maintaining retinal ganglion cell health and that deletion of SPP1 (secreted phosphoprotein 1, or osteopontin) from astrocytes leads to increased vulnerability of ganglion cells to age, elevated intraocular pressure, and traumatic optic nerve damage. Overexpression of SPP1 slows the age-related decline in ganglion cell numbers and is highly protective of visual function in a mouse model of glaucoma. SPP1 acts by promoting phagocytosis and secretion of neurotrophic factors while inhibiting production of neurotoxic and pro-inflammatory factors. SPP1 up-regulates transcription of genes related to oxidative phosphorylation, functionally enhances mitochondrial respiration, and promotes the integrity of mitochondrial microstructure. SPP1 increases intracellular ATP concentration via up-regulation of VDAC1.

PURPOSE: To determine the relative contribution of intraocular lens (IOL) calculation accuracy and ocular growth variability to the long-term refractive error predicted following pediatric cataract surgery. METHODS: Pseudophakic eyes of children enrolled in the Infant Aphakia Treatment Study (IATS) were included in this study. Initial absolute prediction error (APE) and 10-year APE were calculated using the initial biometry, IOL parameters, postoperative refractions, and mean rate of refractive growth. The cohort was divided into children with a low-initial APE (≤1.0 D) and a high-initial APE ( >1.0 D). The 10-year APE was compared between the two groups using the Mann-Whitney U test. Linear regression was used to estimate the variability in prediction error explained by the initial IOL calculation accuracy. RESULTS: Forty-two children with IOL placement in infancy were included. Seventeen eyes had a low initial APE, and 25 eyes had a high initial APE. There was no significant difference in APE 10 years following surgery between individuals with a low initial APE (median, 2.67 D; IQR, 1.61-4.12 D) and a high initial APE (median, 3.45 D; IQR, 1.64-5.10 D) (P = 0.7). Initial prediction error could explain 12% of the variability in the prediction error 10 years following surgery. CONCLUSIONS: IOL calculation accuracy contributed minimally to the refractive error predicted 10 years after cataract surgery in the setting of high variability in the rate of refractive growth.

PURPOSE: The purpose of this study was to assess the potential of new lipoglycopeptides as novel topical therapies for improved treatment of recalcitrant ocular infections. We evaluated the in vitro antimicrobial activity of oritavancin, dalbavancin, and telavancin compared with vancomycin (VAN) against a large collection of ocular staphylococcal isolates and their cytotoxicity on human corneal epithelial cells (HCECs). METHODS: Antimicrobial susceptibility testing was performed by broth microdilution against 223 Staphylococcus spp. clinical isolates. Time-kill kinetics were determined for methicillin-resistant strains of Staphylococcus aureus (MRSA) (n = 2) and Staphylococcus epidermidis (MRSE) (n = 1). In vitro cytotoxicity assays were performed with AlamarBlue and live/dead staining on HCECs. RESULTS: All new lipoglycopeptides showed strong in vitro potency against ocular staphylococci, including multidrug-resistant MRSA strains, with dalbavancin showing a slightly higher potency overall [minimum inhibitory concentration (MIC)90 0.06 μg/mL] compared with telavancin and oritavancin (MIC90 0.12 μg/mL), whereas VAN had the lowest potency (MIC90 2 μg/mL). Oritavancin exerted rapid bactericidal activity within 1 h for MRSA and 2 h for MRSE. All other drugs were bactericidal within 24 h. At a concentration commonly used for topical preparations (25 mg/mL), cytotoxicity was observed for VAN after 5 min of incubation, whereas reduction in HCEC viability was not seen for telavancin and was less affected by oritavancin and dalbavancin. Cytotoxicity at 25 mg/mL was seen for all drugs at 30 and 60 min but was significantly reduced or undetected for lower concentrations. CONCLUSIONS: Our study demonstrates that new lipoglycopeptides have substantially better in vitro antimicrobial activity against ocular staphylococcal isolates compared with VAN, with a similar or improved toxicity profile on HCECs.

PURPOSE: To determine prevalence of probable polypoidal choroidal vasculopathy (PCV) among White patients with neovascular age-related macular degeneration (nAMD) using non-indocyanine green angiography (ICGA) criteria DESIGN: Multicenter, multinational, retrospective, cross-sectional study. METHODS: A total of 208 treatment-naive eyes from Hispanic and non-Hispanic White individuals diagnosed with nAMD were included. All underwent color fundus photography (CFP), optical coherence tomography (OCT), and fluorescein angiography (FFA). De-identified images of study eyes were sent to 2 groups of graders. Group 1 reviewed CFP, OCT, and FFA to confirm nAMD diagnosis. Group 2 reviewed CFP and OCT to determine highly suggestive features for PCV. Probable PCV diagnosis defined as the presence of ≥2 of 4 highly suggestive features for PCV: notched or fibrovascular pigment epithelial detachment (PED) on CFP, sharply-peaked PED, notched PED, and hyperreflective ring on OCT. RESULTS: Eleven eyes were excluded because of poor image quality (6) or non-nAMD diagnosis (5). Of 197 eligible eyes (197 patients), the mean age (SD) was 78.8 years (8.9), 44.2% were men, 26.4% were Hispanic, and 73.6% were non-Hispanic White individuals; 41.1%, 23.4%, 9.1%, and 2.5% had ≥1, ≥2, ≥3, and 4 highly suggestive features. Results showed that 23.4% (95% CI, 17.6%-29.9%) had probable PCV diagnosis. Predominantly occult CNV was more frequently found in probable PCV than nAMD subgroup (84.8% vs 64.9%, P = .01). Hispanic White individuals had a lower prevalence of probable PCV than non-Hispanic White individuals (9.6% vs 28.2%, P = .006) CONCLUSIONS: These findings suggest that probable PCV occurs between 17.6% and 29.9% in White individuals with nAMD, and more commonly in non-Hispanic than in Hispanic White individuals.

Infectious uveitis is a sight-threatening infection commonly caused by herpesviruses. Vitreous humor is often collected for molecular confirmation of the causative agent during vitrectomy and mixed in large volumes of buffered saline, diluting the pathogen load. Here, we explore affinity-capture hydrogel particles (Nanotrap®) to concentrate low abundant herpesviruses from diluted vitreous. Simulated samples were prepared using porcine vitreous spiked with HSV-1, HSV-2, VZV and CMV at 105 copies/mL. Pure undiluted samples were used to test capturing capability of three custom Nanotrap particles (red, white and blue) in a vitreous matrix. We found that all particles demonstrated affinity to the herpesviruses, with the Red Particles having both good capture capability and ease of handling for all herpesviruses. To mimic diluted vitrectomy specimens, simulated-infected vitreous were then serially diluted in 7 mL TE buffer. Diluted samples were subjected to an enrichment protocol using the Nanotrap Red particles. Sensitivity of pathogen detection by qPCR in diluted vitreous increased anywhere between 2.3 to 26.5 times compared to non-enriched specimens. This resulted in a 10-fold increase in the limit of detection for HSV-1, HSV-2 and VZV. These data demonstrated that Nanotrap particles can capture and concentrate HSV-1, HSV-2, VZV and CMV in a vitreous matrix.

OBJECTIVE: To describe the relationships between the cumulative incidences of long-term complications in individuals with type 1 diabetes (T1D) and assess whether observed associations are independent of age, duration of diabetes, and glycemic levels. METHODS: Proliferative diabetic retinopathy (PDR), clinically significant macular edema (CSME), reduced estimated glomerular filtration rate (eGFR), amputations, cardiovascular disease (CVD), and mortality were assessed in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study over ∼30 years. RESEARCH DESIGN AND RESULTS: The cumulative incidence of complications ranged from 3% (amputations) to 37% (CSME). There were large differences in the cumulative incidence of PDR between participants with versus without prior CSME (66% vs. 15%), reduced eGFR (59% vs. 29%), and amputation (68% vs. 32%); reduced eGFR with or without prior PDR (25% vs. 9%), amputation (48% vs. 13%), and CVD (30% vs. 11%); CVD with or without prior reduced eGFR (37% vs. 14%) and amputation (50% vs. 16%); and mortality with or without prior reduced eGFR (22% vs. 9%), amputation (35% vs. 8%), and CVD (25% vs. 8%). Adjusted for age, duration of T1D, and mean updated HbA1c, the complications and associations with higher risk included PDR with CSME (hazard ratio [HR] 1.88; 95% CI 1.42, 2.50), reduced eGFR (HR 1.41; 95% CI 1.01, 1.97), and CVD (HR 1.43; 95% CI 1.06, 1.92); CSME with higher risk of PDR (HR 3.94; 95% CI 3.18 4.89), reduced eGFR (HR 1.49; 95% CI 1.10, 2.01), and CVD (HR 1.35; 95% CI 1.03, 1.78); reduced eGFR with higher risk of CVD (HR 2.09; 95% CI 1.44, 3.03), and death (HR 3.40; 95% CI 2.35, 4.92); amputation(s) with death (HR 2.97; 95% CI 1.70, 2.90); and CVD with reduced eGFR (HR 1.59; 95% CI 1.08, 2.34) and death (HR 1.95; 95% CI 1.32, 2.90). CONCLUSIONS: Long-term micro- and macrovascular complications and mortality are highly correlated. Age, diabetes duration, and glycemic levels do not completely explain these associations.

PURPOSE: To review the current published literature on the utility of corneal hysteresis (CH) to assist the clinician in the diagnosis of glaucoma or in the assessment of risk for disease progression in existing glaucoma patients. METHODS: Searches of the peer-reviewed literature in the PubMed database were performed through July 2022. The abstracts of 423 identified articles were examined to exclude reviews and non-English articles. After inclusion and exclusion criteria were applied, 19 articles were selected, and the panel methodologist rated them for level of evidence. Eight articles were rated level I, and 5 articles were rated level II. The 6 articles rated level III were excluded. RESULTS: Corneal hysteresis is lower in patients with primary open-angle glaucoma, primary angle-closure glaucoma, pseudoexfoliative glaucoma, and pseudoexfoliation syndrome compared with normal subjects. Interpretation of low CH in patients with high intraocular pressure (IOP) or on topical hypotensive medications is complicated by the influence of these parameters on CH measurements. However, CH is also lower in treatment-naïve, normal-tension glaucoma patients compared with normal subjects who have a similar IOP. In addition, lower CH is associated with an increased risk of progression of glaucoma based on visual fields or structural markers in open-angle glaucoma patients, including those with apparently well-controlled IOP. CONCLUSIONS: Corneal hysteresis is lower in glaucoma patients compared with normal subjects, and lower CH is associated with an increased risk of disease progression. However, a causal relationship remains to be demonstrated. Nevertheless, measurement of CH complements current structural and functional assessments in determining disease risk in glaucoma suspects and patients. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

PURPOSE: To report the indications, operative strategies, and surgical outcomes of patients who undergo vertical and horizontal rectus muscle surgery for incomitant strabismus despite being orthophoric in primary gaze. DESIGN: Retrospective, interventional case series. METHODS: • Setting: Academic practice at Boston Children's Hospital. • Patient Population: Eight orthophoric patients who underwent strabismus surgery to treat vertical/horizontal incomitance. • Observation Procedures: Review of surgical strategies, strabismus measurements in diagnostic gaze positions, development of post-op diplopia. • Main Outcome Measures: Preserved single vision in primary gaze, comitance, reoperation rate, and patient/surgeon satisfaction. RESULTS: Surgical strategies included 1) simultaneous recession of ipsilateral antagonist rectus muscles; 2) recession or resection of one rectus muscle with balancing surgery on the fellow eye; 3) restricting range of one muscle (combined resection and recession or posterior fixation suture); 4) creating an acceptable deviation in primary gaze. Mean follow-up was 5.4 months (median, 2 months; range, 2-25). No patient had new-onset primary gaze diplopia. Median incomitance improved by 9.5 PD. No patient required additional surgery. Patient satisfaction and surgeon assessment of outcomes were high. CONCLUSIONS: Although the risk of operating on orthophoric patients with incomitant strabismus may discourage surgeons from offering treatment, the use of specific strategies to address incomitance can preserve alignment in primary gaze while improving patient satisfaction. These strategies may also benefit patients with incomitant strabismus that is symptomatic in primary gaze.

A 77-year-old Asian female with a history of left orbit exenteration and lid-sparing reconstruction for recurrent sebaceous carcinoma presented with fluid-like sensation of the left orbit. Magnetic resonance imaging (MRI) demonstrated bright T2 signal and a cyst-like cavity within the exenterated orbit. Decision was made to proceed with surgical exploration and excision. A calcified, bone-like cavity was encountered intraoperatively and removed. Histopathology revealed dense fibrous connective tissue with areas of calcification without osseous metaplasia, suggestive of retained blood in the orbit that underwent dystrophic calcification. This case report illustrates a rare occurrence of a bone-like calcific cyst following exenteration.

PURPOSE: To investigate a causal relationship between Vitamin D levels and non-infectious uveitis and scleritis using Mendelian randomization (MR) techniques. DESIGN: Two-sample Mendelian randomization case-control study. METHODS: The study setting was a biobank of an academic, integrated health care system. The patient population comprised 375 case patients with a non-infectious uveitis and/or scleritis diagnosis and no diagnosis of infectious, trauma-related, or drug-induced uveitis/scleritis. In addition, there were 4167 controls with no uveitis or scleritis diagnosis. Causal effect estimates of low 25-hydroxy Vitamin D (25OHD) on uveitis/scleritis risk were calculated. RESULTS: We found an association of genetically decreased 25OHD with uveitis/scleritis risk (odds ratio [OR] = 2.16, 95% CI = 1.01-4.64, P = .049, per SD decrease in log25OHD). In a first sensitivity MR analysis excluding the genetic variants that are unlikely to have a role in biologically active 25OHD, effect estimates were consistent with those from the primary analysis (OR = 2.38, 95% CI =1.06-5.36, P = 0.035, per SD of log25OHD). Furthermore, in a second sensitivity analysis using only the 6 variants within the CYP2R1 locus (which encodes 25OHD hydroxylase, the liver enzyme responsible for converting Vitamin D to 25OHD), genetically decreased 25OHD was strongly associated with increased uveitis/scleritis risk (OR = 6.42, 95% CI = 3.19-12.89, P = 1.7 × 10-7, per SD of log25OHD). CONCLUSIONS: Our findings suggest a causal relationship between low Vitamin D levels and higher risk of non-infectious uveitis and scleritis. Vitamin D supplementation may be a low-cost, low-risk intervention to mitigate non-infectious uveitis and scleritis risk, and should be explored in a prospective trial.

PURPOSE: To determine the sensitivity and positive predictive value (PPV) of a contiguous, perineural retinal vascular leakage fluorescein angiography (FA) pattern in birdshot chorioretinopathy (BSCR) patients. METHODS: Patients with BSCR and other posterior uveitis/retinal vasculitis and a FA were identified. Two graders reviewed the first FA for leakage primarily around the optic nerve and along the larger arcade vessels. We compared the rates of this pattern in BSCR and non-BSCR patients and calculated sensitivity and PPV. We compared clinical characteristics of BSCR patients with and without this pattern. RESULTS: 64 BSCR and 98 non-BSCR patients were identified. The FA pattern's sensitivity, specificity, and PPV were 57.8%, 91.8%, and 82.2%. This pattern was significantly more common in BSCR patients earlier in their disease (p = .004). CONCLUSIONS: A contiguous, perineural retinal vascular leakage FA pattern can help identify potential BSCR patients for further testing. This pattern is more common closer to symptom onset.

Pediatric glaucoma is a constellation of challenging ophthalmic conditions that, left untreated, can result in irreversible vision loss. The mainstay of treatment for primary congenital glaucoma and select secondary glaucoma subtypes is angle surgery, either trabeculotomy or goniotomy. More recently, MIGS devices have been utilized to enhance the efficacy of these procedures. Despite the high success rates of these primary surgical options, refractory cases are challenging to manage. There is no consensus on the next step of treatment following primary angle surgery. Glaucoma drainage devices and trabeculectomies have been the traditional options, with laser treatment reserved for more severe cases. The benefits and disadvantages of each of these options are discussed.

This study aimed to develop a miltefosine-eluting contact lens (MLF-CL) device that would allow sustained and localized miltefosine release for the treatment of Acanthamoeba keratitis. MLF-CLs were produced in three different miltefosine doses by solvent-casting a thin miltefosine-polymer film around the periphery of a methafilcon hydrogel, which was then lathed into a contact lens. During seven days of in vitro testing, all three formulations demonstrated sustained release from the lens at theoretically therapeutic levels. Based on the physicochemical characterization of MLF-CLs, MLF-CL's physical properties are not significantly different from commercial contact lenses in terms of light transmittance, water content and wettability. MLF-CLs possessed a slight reduction in compression modulus that was attributed to the inclusion of polymer-drug films but still remain within the optimal range of soft contact lenses. In cytotoxicity studies, MLF-CL indicated up to 91% viability, which decreased proportionally as miltefosine loading increased. A three-day biocompatibility test on New Zealand White rabbits revealed no impact of MLF-CLs on the corneal tissue. The MLF-CLs provided sustained in vitro release of miltefosine for a week while maintaining comparable physical features to a commercial contact lens. MLF-CL has a promising potential to be used as a successful treatment method for Acanthamoeba keratitis.

OBJECTIVE: To determine whether individuals with type 1 diabetes (T1D) who develop any retinopathy at any time prior to 5 years of diabetes duration have an increased subsequent risk for further progression of retinopathy or onset of proliferative diabetic retinopathy (PDR), clinically significant macular edema (CSME), diabetes-related retinal photocoagulation, or anti-vascular endothelial growth factor injections. Additionally, to determine the influence of HbA1c and other risk factors in these individuals. RESEARCH DESIGN AND METHODS: Diabetic retinopathy (DR) was assessed longitudinally using standardized stereoscopic seven-field fundus photography at time intervals of 6 months to 4 years. Early-onset DR (EDR) was defined as onset prior to 5 years of T1D duration. Cox models assessed the associations of EDR with subsequent risk of outcomes. RESULTS: In unadjusted models, individuals with EDR (n = 484) had an increased subsequent risk of PDR (hazard ratio [HR] 1.51 [95% CI 1.12, 2.02], P = 0.006), CSME (HR 1.44 [1.10, 1.88], P = 0.008), and diabetes-related retinal photocoagulation (HR 1.48 [1.12, 1.96], P = 0.006) compared with individuals without EDR (n = 369). These associations remained significant when adjusted for HbA1c, but only the association with PDR remained significant after adjustment for age, duration of T1D, HbA1c, sex, systolic/diastolic blood pressure, pulse, use of ACE inhibitors, albumin excretion rate, and estimated glomerular filtration rate (HR 1.47 [95% CI 1.04, 2.06], P = 0.028). CONCLUSIONS: These data suggest that individuals with any sign of retinopathy within the first 5 years of T1D onset may be at higher risk of long-term development of advanced DR, especially PDR. Identification of early-onset DR may influence prognosis and help guide therapeutic management to reduce the risk of future visual loss in these individuals.