PURPOSE: To assess baseline ocular biometric risk factors for progression from primary angle closure suspect (PACS) to primary angle closure (PAC) or acute angle closure (AAC). DESIGN: Prospective, observational study. PARTICIPANTS: Six hundred forty-three mainland Chinese with untreated PACS. METHODS: Participants underwent baseline clinical examinations, including gonioscopy, anterior segment OCT (AS-OCT) imaging, and A-scan ultrasound biometry as part of the Zhongshan Angle Closure Prevention (ZAP) Trial. Primary angle closure suspect was defined as an inability to visualize pigmented trabecular meshwork in 2 or more quadrants based on static gonioscopy. Primary angle closure was defined as development of intraocular pressure above 24 mmHg or peripheral anterior synechiae. Progression was defined as development of PAC or an AAC attack. Multivariable logistic regression models were developed to assess biometric risk factors for progression. MAIN OUTCOME MEASURES: Six-year progression from PACS to PAC or AAC. RESULTS: Six hundred forty-three untreated eyes (609 nonprogressors, 34 progressors) of 643 participants were analyzed. In a multivariable model with continuous parameters, narrower horizontal angle opening distance of 500 μm from the scleral spur (AOD500; odds ratio [OR], 1.10 per 0.01-mm decrease; P = 0.03), flatter horizontal iris curvature (IC; OR, 1.96 per 0.1-mm decrease; P = 0.01), and older age (OR, 1.11 per 1-year increase; P = 0.01) at baseline were associated significantly with progression (area under the receiver operating characteristic curve [AUC], 0.73). Smaller cumulative gonioscopy score was not associated with progression (OR, 1.03 per 1-modified Shaffer grade decrease; P = 0.85) when replacing horizontal AOD500 in the multivariable model. In a separate multivariable model with categorical parameters, participants in the lowest quartile of horizontal AOD500 (OR, 3.10; P = 0.002) and IC (OR, 2.48; P = 0.014) measurements and 59 years of age or older (OR, 2.68; P = 0.01) at baseline showed higher odds of progression (AUC, 0.72). CONCLUSIONS: Ocular biometric measurements can help to risk-stratify patients with early angle closure for more severe disease. Anterior segment OCT measurements of biometric parameters describing the angle and iris are predictive of progression from PACS to PAC or AAC, whereas gonioscopy grades are not.

BACKGROUND: Dry eye disease (DED) is a multifactorial disease of the tear film and ocular surface. It causes ocular symptoms, reduced quality of life and a considerable economic burden on society. Prolonged use of visual display terminals (VDTs) has been suggested as an important risk factor for DED. PURPOSE: This review aims to study the association between DED and VDT use with an emphasis on the prevalence of DED among VDT users and harmful daily duration of VDT use. METHODS: A PubMed search was conducted and yielded 57 relevant articles based on a set of inclusion and exclusion criteria. The studies were subclassified according to study design. RESULTS: The far majority of the studies showed an association between VDT use and DED or DED-related signs and symptoms. The prevalence of definite or probable DED in VDT and office workers ranged from 26% to 70%, with as few as 1-2 hr of VDT exposure per day being associated with DED. CONCLUSION: VDT use is strongly associated with DED. VDT-associated DED is prevalent, but the exact prevalence needs to be further elucidated using standardized DED diagnosis criteria. Furthermore, a safe lower limit of daily VDT use has yet to be established. More research is needed on the effect of digitalization and digital transformation, which are particularly high during the time of the COVID-19 pandemic.

Full-thickness wounds to the eye can lead to serious vision impairment. Current standards of care (from suturing to tissue transplantation) usually require highly skilled surgeons and use of an operating theater. In this study, we report the synthesis, optimization, and in vitro and ex vivo testing of photocrosslinkable hydrogel-based adhesive patches that can easily be applied to globe injuries or corneal incisions. According to the type and concentration of polymers used in the adhesive formulations, we were able to finely tune the physical properties of the bioadhesive including viscosity, elastic modulus, extensibility, ultimate tensile strength, adhesion, transparency, water content, degradation time, and swellability. Our in vitro studies showed no sign of cytotoxicity of the hydrogels. Moreover, the hydrogel patches showed higher adhesion on freshly explanted pig eyeballs compared to a marketed ocular sealant. Finally, ex vivo feasibility studies showed that the hydrogel patches could seal complex open-globe injuries such as large incision, cruciform injury, and injury associated with tissue loss. These results suggest that our photocrosslinkable hydrogel patch could represent a promising solution for the sealing of open-globe injuries or surgical incisions. STATEMENT OF SIGNIFICANCE: Current management of severe ocular injuries require advanced surgical skills and access to an operating theater. To address the need for emergent management of wounds that cannot be handled in the operating room, surgical adhesives have gained popularity, but none of the currently available adhesives have optimal bioavailability, adhesive or mechanical properties. This study describes the development, optimization and testing of a light-sensitive adhesive patch that can easily be applied to the eye. After solidification using visible light, the patch shows no toxicity and is more adherent to the tissue than a marketed sealant. Thus this technology could represent a promising solution to stabilize ocular injuries in emergency settings before definitive surgical repair.

PURPOSE: To determine if treatment with a photobiomodulation (PBM) device results in greater improvement in central subfield thickness (CST) than placebo in eyes with center-involved diabetic macular edema (CI-DME) and good vision. DESIGN: Phase 2 randomized clinical trial. PARTICIPANTS: Participants had CI-DME and visual acuity (VA) 20/25 or better in the study eye and were recruited from 23 clinical sites in the United States. METHODS: One eye of each participant was randomly assigned 1:1 to a 670-nm light-emitting PBM eye patch or an identical device emitting broad-spectrum white light at low power. Treatment was applied for 90 seconds twice daily for 4 months. MAIN OUTCOME MEASURES: Change in CST on spectral-domain OCT at 4 months. RESULTS: From April 2019 to February 2020, 135 adults were randomly assigned to either PBM (n = 69) or placebo (n = 66); median age was 62 years, 37% were women, and 82% were White. The median device compliance was 92% with PBM and 95% with placebo. OCT CST increased from baseline to 4 months by a mean (SD) of 13 (53) μm in PBM eyes and 15 (57) μm in placebo eyes, with the mean difference (95% confidence interval [CI]) being -2 (-20 to 16) μm (P = 0.84). CI-DME, based on DRCR Retina Network sex- and machine-based thresholds, was present in 61 (90%) PBM eyes and 57 (86%) placebo eyes at 4 months (adjusted odds ratio [95% CI] = 1.30 (0.44-3.83); P = 0.63). VA decreased by a mean (SD) of -0.2 (5.5) letters and -0.6 (4.6) letters in the PBM and placebo groups, respectively (difference [95% CI] = 0.4 (-1.3 to 2.0) letters; P = 0.64). There were 8 adverse events possibly related to the PBM device and 2 adverse events possibly related to the placebo device. None were serious. CONCLUSIONS: PBM as given in this study, although safe and well-tolerated, was not found to be effective for the treatment of CI-DME in eyes with good vision.

PURPOSE: To calculate costs required to prevent center-involved diabetic macular edema (CI-DME) or proliferative diabetic retinopathy (PDR), and to improve the diabetic retinopathy severity score (DRSS) with intravitreal anti-VEGF injections, as reported for aflibercept in 2 randomized control trials. DESIGN: Cost-effectiveness analysis modeling based on published data. SUBJECTS: None. METHODS: Results from PANORAMA and the Diabetic Retinopathy Clinical Research Network Protocol W were analyzed. Parameters collected included DRSS, risk reduction of PDR, risk reduction of CI-DME, and the number of treatments required. Costs were modeled based on 2020 Medicare reimbursement data practice settings of hospital-based facility and nonfacility. MAIN OUTCOME MEASURES: Cost to prevent cases of PDR and CI-DME and to improve DRSS stage. RESULTS: Over 2 years in Protocol W, the cost required to prevent 1 case of PDR was $83 000 ($72 400) in the facility (nonfacility) setting; in PANORAMA, the corresponding 2-year costs were $89 400 ($75 000) for the 2-mg aflibercept every 16 weeks (2Q16) arm, and $91 200 ($89 900) for the 2-mg aflibercept every 8 weeks as needed (2Q8PRN) arm. To prevent 1 case of CI-DME with vision loss in Protocol W, the cost was $154 000 ($133 000). For all CI-DME, with and without vision loss, in PANORAMA, the costs to prevent a case were $70 900 ($59 500) for the 2Q16 arm and $90 000 ($88 800) for the 2Q8PRN arm. In Protocol W, the overall accumulated total for cost/DRSS unit change at the 2-year point for facility (nonfacility) setting was $2700 ($2400)/DRSS. In the first year alone, it was $2100 ($1800)/DRSS and in the second year, it was $6100 ($5300)/DRSS. CONCLUSIONS: There is a considerable cost associated with the prevention of PDR and CI-DME with intravitreal aflibercept injections. A price per unit of change in DRSS is a new parameter that might serve as a benchmark in future utility analyses that could be used to bring the perspective to cost-utility considerations.

Axons are a unique cellular structure that allows for the communication between neurons. Axon damage compromises neuronal communications and often leads to functional deficits. Thus, developing strategies that promote effective axon regeneration for functional restoration is highly desirable. One fruitful approach is to dissect the regenerative mechanisms used by some types of neurons in both mammalian and nonmammalian systems that exhibit spontaneous regenerative capacity. Additionally, numerous efforts have been devoted to deciphering the barriers that prevent successful axon regeneration in the most regeneration-refractory system-the adult mammalian central nervous system. As a result, several regeneration-promoting strategies have been developed, but significant limitations remain. This review is aimed to summarize historic progression and current understanding of this exciting yet incomplete endeavor.

BACKGROUND: Retinovascular changes are reported on fundus imaging in schizophrenia (SZ). This is the first study to use swept-source optical coherence tomography angiography (OCT-A) to comprehensively examine retinal microvascular changes in SZ. METHODS: This study included 30 patients with SZ/schizoaffective disorder (8 early and 15 chronic) and 22 healthy controls (HCs). All assessments were performed at Beth Israel Deaconess Medical Center and Massachusetts Eye and Ear. All participants underwent swept-source OCT-A of right (oculus dextrus [OD]) and left (oculus sinister [OS]) eye, clinical, and cognitive assessments. Macular OCT-A images (6 × 6 mm) were collected with the DRI Topcon Triton for superficial, deep, and choriocapillaris vascular regions. Microvasculature was quantified using vessel density (VD), skeletonized vessel density (SVD), fractal dimension (FD), and vessel diameter index (VDI). RESULTS: Twenty-one HCs and 26 SZ subjects were included. Compared to HCs, SZ patients demonstrated higher overall OD superficial SVD, OD choriocapillaris VD, and OD choriocapillaris SVD, which were primarily observed in the central, central and outer superior, and central and outer inferior/superior, respectively. Early-course SZ subjects had significantly higher OD superficial VD, OD choriocapillaris SVD, and OD choriocapillaris FD compared to matched HCs. Higher bilateral (OU) superficial VD correlated with lower Positive and Negative Syndrome Scale (PANSS) positive scores, and higher OU deep VDI was associated with higher PANSS negative scores. CONCLUSIONS AND RELEVANCE: These results suggest the presence of microvascular dysfunction associated with early-stage SZ. Clinical associations with microvascular alterations further implicate this hypothesis, with higher measures being associated with worse symptom severity and functioning in early stages and with lower symptom severity and better functioning in later stages.

CONTEXT.—: Conjunctival melanocytic lesions consist of a variety of neoplastic and nonneoplastic conditions. These include benign processes such as primary intraepithelial hypermelanosis and melanocytic hyperplasia, secondary forms of intraepithelial hypermelanosis and melanocytic hyperplasia, melanocytic nevi, melanocytic proliferations with malignant potential, and melanoma. OBJECTIVE.—: To provide a concise yet comprehensive resource regarding the histopathologic diagnosis of conjunctival melanocytic lesions. We aim to detail and clarify the numerous classification schemes that exist for junctional melanocytic proliferations of the conjunctiva (known as primary acquired melanosis or PAM; also termed conjunctival melanocytic intraepithelial neoplasia or C-MIN). Although not uniformly adopted, C-MIN is classified by using a numeric system based on a defined set of criteria. A less complex scheme (conjunctival melanocytic intraepithelial lesion or CMIL) has recently been proposed by the World Health Organization. Additionally, we aim to update the reader regarding molecular features and prognostic indicators. DATA SOURCES.—: Peer-reviewed literature and archived cases for illustration. CONCLUSIONS.—: Accurate histologic classification is essential, as PAM/C-MIN/CMILs that have a significant potential to progress to invasive melanoma may be clinically indistinguishable from low-risk lesions. Conjunctival melanoma (CM) more closely resembles cutaneous melanoma in terms of its pathogenesis and molecular features, compared to melanoma arising at other mucosal sites or to uveal melanoma. Depth of invasion and ulceration status, among other factors, have emerged as important prognostic indicators in CM. Sentinel lymph node biopsy may provide further prognostic information. Lastly, integration of pathologic and clinical findings is essential at this anatomically sensitive location to determine appropriate clinical management.

PURPOSE: To review the evidence on the safety and efficacy of current anti-vascular endothelial growth factor (VEGF) and intravitreal corticosteroid pharmacotherapies for the treatment of diabetic macular edema (DME). METHODS: Literature searches were last conducted on May 13, 2020, in the PubMed database with no date restrictions and limited to articles published in English. The combined searches yielded 230 citations, of which 108 were reviewed in full text. Of these, 31 were deemed appropriate for inclusion in this assessment and were assigned a level of evidence rating by the panel methodologist. RESULTS: Only the 21 articles with level I evidence were included in this assessment. Seventeen articles provided level I evidence for 1 or more anti-VEGF pharmacotherapies, including ranibizumab (14), aflibercept (5), and bevacizumab (2) alone or in combination with other treatments for DME. Level I evidence was identified in 7 articles on intravitreal corticosteroid therapy for treatment of DME: triamcinolone (1), dexamethasone (4), and fluocinolone acetonide (2). CONCLUSIONS: Review of the available literature indicates that intravitreal injections of anti-VEGF agents and corticosteroids are efficacious treatments for DME. Elevated intraocular pressure and cataract progression are important potential complications of corticosteroid therapy. Further evidence is required to assess the comparative efficacy of these therapies. Given the limited high-quality comparative efficacy data, choice of therapy must be individualized for each patient and broad therapeutic access for patients is critical to maximize outcomes.

PURPOSE: To review the clinical features, microbiology, management, and incidence of bacterial dacryoadenitis at our institution. METHODS: This was a case series examining patients with bacterial dacryoadenitis from 2004 to 2020. Charts were reviewed for demographics, comorbidities, presenting symptoms and signs, radiology, microbiology, and management. Main outcomes included need for surgical intervention or inpatient admission. RESULTS: Forty-five patients with bacterial dacryoadenitis had a mean age of 46.1 years. Presenting symptoms included eyelid edema (100%), extraocular motility restriction (53.3%), and purulent discharge (75.5%). Based on computed tomography or magnetic resonance imaging, 9 (20.5%) patients presented with definite abscess and 15 (34%) presented with a phlegmon or early abscess. Eleven patients (24.4%) required surgical drainage. Twenty patients (44.4%) required admission, for an average stay of 4 days (range 2-8 days). Common organisms included Haemophilus influenzae, Streptococcus pneumoniae, and Staphylococcus aureus. Presence of an early abscess or phlegmon correlated with need for drainage (p < 0.01). Extraocular motility restriction correlated with need for drainage (p = 0.02) and admission (p = 0.05). The incidence of bacterial dacryoadenitis at our institution increased as a percentage of confirmed dacryoadenitis cases; from 2004 to 2010 the incidence was 0 to 9.1% per year, while from 2010 to 2019 the incidence ranged from 7.7 to 36.2%. In 2019, our institution had 17 cases (incidence 36.2%) of bacterial dacryoadenitis. CONCLUSIONS: Bacterial dacryoadenitis is a major cause of dacryoadenitis, and its incidence may be increasing. It can resolve with minimal complications if managed appropriately, although some patients may require surgical drainage or admission for intravenous antibiotics.