Engineered polymer vesicles, termed as polymersomes, confer a flexibility to control their structure, properties, and functionality. Self‐assembly of amphiphilic copolymers leads to vesicles ...consisting of a hydrophobic bilayer membrane and hydrophilic core, each of which is loaded with a wide array of small and large molecules of interests. As such, polymersomes are increasingly being studied as carriers of imaging probes and therapeutic drugs. Effective delivery of polymersomes necessitates careful design of polymersomes. Therefore, this review article discusses the design strategies of polymersomes developed for enhanced transport and efficacy of imaging probes and therapeutic drugs. In particular, the article focuses on overviewing technologies to regulate the size, structure, shape, surface activity, and stimuli‐ responsiveness of polymersomes and discussing the extent to which these properties and structure of polymersomes influence the efficacy of cargo molecules. Taken together with future considerations, this article will serve to improve the controllability of polymersome functions and accelerate the use of polymersomes in biomedical applications.
Polymersomes, as engineered polymer vesicles, are well received as efficient carriers for the delivery of diagnostic and therapeutic molecules. Chemical modifications to self‐assembling polymers allow customization of nanosized carriers for a wide variety of clinical applications. This review highlights the critical design features and discusses the current efforts to engineer polymersomes for the next generation of nanomedicine.
Thyroid eye disease (TED) is a disfiguring disease that can lead to neuro-ophthalmic manifestations including diplopia and optic neuropathy. The aim of this review is to shed light on the diagnosis ...of TED based on clinical examination findings and diagnostic imaging. We will also discuss gold standard as well as newly emerging therapies for TED.
We discussed diagnostic criteria for TED and differentiating TED from other causes of binocular diplopia. We also reviewed the pathophysiology and differential diagnoses for dysthyroid optic neuropathy as well as recent developments on controversial causes. New imaging techniques are available for evaluation and prognosis of TED comorbidities. Most of the recent developments in TED have been focused on new treatment modalities that have thus far had promising results. We reviewed recently approved and novel potential therapies that are helpful in treating both diplopia and dysthyroid optic neuropathy.
TED is a complicated disorder with many clinical manifestations as well as treatment modalities. Our aim of this review was to outline new developments in the diagnosis and management of TED.
To assess the efficacy of endonasal dacryocystorhinostomy (DCR) compared with external DCR.
A literature search was conducted in the PubMed database in March 2016 and updated in October 2017 and ...February 2019. The search strategy was designed to update the first Ophthalmic Technology Assessment on endonasal DCR from 2001 by identifying new peer-reviewed human studies reported since 2000 in the English language that compare results of endonasal DCR with those of external DCR. The searches yielded 169 articles. Of these, 13 met the inclusion criteria and were assigned a level of evidence rating.
Six of the 13 studies included in this assessment were rated level II and 7 were rated level III. Three of the 13 studies drew conclusions based on statistically significant results, but all of these were level III evidence. Two of these significant studies demonstrated lesser efficacy of endonasal laser DCR (63%-64%) compared with external DCR (94%; P = 0.0002, 0.024). The third study reported that nonlaser endonasal DCR was superior to external DCR (84% vs. 70%; P = 0.03). The remainder of the studies did not find statistically significant differences in success rates between the 2 techniques.
Limited data suggest that laser endonasal DCR may be less effective than external DCR. Existing data are inadequate to draw conclusions about whether endonasal DCR is superior to, equivalent to, or inferior to the gold standard external DCR.
Ocular surface disease (OSD) in the setting of thyroid eye disease (TED) is traditionally thought of as a natural consequence of anatomical changes such as proptosis and corneal exposure. However, a ...growing body of research suggests that ocular surface inflammation and multi-factorial changes to the homeostasis of the ocular surface contribute substantially to the OSD seen in TED patients. In this paper we review the existing literature which highlights the work and existing theories underlying this new paradigm shift.
To compare the motility and complication rates of porous and nonporous implants after enucleation surgery.
Literature searches of the PubMed and Cochrane Library databases were last performed in ...February 2017 to identify studies published between 2003 and 2017 on outcomes after enucleation surgeries in which a variety implants were used. The searches were limited to the English language with abstracts and yielded 43 articles, which the Ophthalmic Technology Assessment Committee Oculoplastics and Orbit Panel reviewed for relevancy. Twenty-five articles were considered to have met the search strategy, and the panel methodologist assigned ratings to them according to the level of evidence.
Only 2 of the 25 articles identified met the criteria for level I evidence. Eighteen of the studies did not assess motility after enucleation surgery, and the 7 that did evaluate this metric involved porous implants. The studies that analyzed this outcome reported favorable results, but the results were not uniformly based on objective analysis. Both porous and nonporous implants were well tolerated, and complication rates were generally low for both types.
In keeping with increasing surgeon preference for porous implants, most studies identified in this literature search involved the use of this type of implant. These implants resulted in excellent motility after enucleation surgery, although many studies did not assess this outcome. Regardless of implant type, major complications were rare, and infection was exceptionally uncommon after enucleation. Given the paucity of data on motility and the absence of direct, objective comparisons of porous and nonporous implants, definitive conclusions about the impact of implant material on motility cannot be made. Since few studies evaluated nonporous implants, direct comparisons cannot be made definitively between implant types, and future investigations are needed to enable a critical assessment.
To review the literature on the efficacy of intense pulsed light (IPL) on the eyelids in the management of meibomian gland disease (MGD) and meibomian gland-related ocular surface disease.
A ...literature search was last conducted on May 15, 2019, in the PubMed and Cochrane Library databases for English-language original research that assessed the effect of IPL on MGD in adult patients. Thirty-three articles were identified, and 12 studies were determined to be relevant to the criteria outlined for assessment. The panel methodologist (V.K.A.) assigned a level of evidence rating to each study; 4 studies were rated level II, and 8 studies were rated level III. Five studies had potential conflicts of interest and design limitations that affected interpretation of results.
All studies documented improvement in clinically meaningful metrics, including tear breakup time (TBUT), corneal staining and eyelid margin measurements, meibum quality, meibomian gland expressability, ocular surface disease index (OSDI), and standard patient evaluation of eye dryness (SPEED) questionnaire scores. Side effects were relatively uncommon but included discomfort, cutaneous erythema, blistering, eyelash loss, and floaters; these were uniformly self-limited.
Although methodological limitations and potential conflicts of interest in some studies raised concern, the existing body of literature demonstrates improvements in the signs and symptoms of MGD after IPL therapy.
Study of human lacrimal cell biology is limited by poor access to tissue samples, heterogeneous cell composition of tissue and a lack of established lacrimal epithelial markers. In order to further ...our understanding of lacrimal cell biology, we sought to find a better marker for human lacrimal epithelial cells, compared to what has been reported in the literature.
We utilized human Muller's muscle conjunctival resection (MMCR) specimens containing accessory lacrimal gland (ALG) and cadaveric main lacrimal gland (MLG) as sources of lacrimal tissue. Candidate markers were sought using human ALG tissue from MMCR specimens, isolated by laser capture microdissection (LCM). Affymetrix® analysis was performed on total RNA isolated from FFPE samples to profile transcription in ALG. MMCR tissue sections were assessed by immunofluorescence using antibodies for histatin-1, lactoferrin, E-cadherin (E-cad) and alpha-smooth muscle actin (ASMA). Reverse transcriptase polymerase chain reaction (RT-PCR) analysis was performed to analyze the expression of histatin-1, E-cad and lactoferrin from cadaveric MLG.
Histatin-1 is expressed in ALG and MLG, localizes to lacrimal epithelium, and to a greater degree than do other putative lacrimal epithelial markers.
Histatin-1 is a good marker for human lacrimal epithelium in ALG and MLG and can be used to identify lacrimal cells in future studies.
To compare the visual outcomes and adverse events associated with optical correction using an intraocular lens (IOL), contact lenses, or spectacles after cataract surgery in children 2 years of age ...or younger.
Literature searches were conducted in PubMed, the Cochrane Library, and the databases of clinical trials in February 2019, without date or language restrictions. The search resulted in 194 potentially relevant citations, and 34 were selected for full-text review. Fourteen studies were determined to be relevant to the assessment criteria and were selected for inclusion in this assessment. The panel methodologist then assigned a level of evidence rating to these studies.
Intraocular lenses were associated with visual outcomes similar to outcomes for contact lenses or spectacles for children who had both bilateral and unilateral cataracts. Intraocular lenses were also associated with an increased risk of visual axis opacities. All treatments were associated with a similar incidence of glaucoma. Although ocular growth was similar for all treatments, infants younger than 6 months who underwent IOL implantation had large myopic shifts that often resulted in high myopia or severe anisometropia later in childhood. Corneal endothelial cell counts were lower in eyes that underwent IOL implantation. The incidence of strabismus was similar with all treatments.
Intraocular lens implantation is not recommended for children 6 months of age or younger because there is a higher incidence of visual axis opacities with this treatment compared with aphakia. The best available evidence suggests that IOL implantation can be done safely with acceptable side effects in children older than 6 months of age. However, the unpredictability of ocular growth means that these children will often have large refractive errors later in childhood that may necessitate an IOL exchange or wearing spectacles or contact lenses with a large refractive correction. In addition, the training and experience of the surgeon as well as ocular and systemic comorbidities should be taken into consideration when deciding whether IOL implantation would be appropriate.
To determine the efficacy and safety of sentinel lymph node biopsy (SLNB) in the management of eyelid and conjunctival malignancy.
A literature search was performed in August 2019 and January 2020 ...for articles published in English in the PubMed and Cochrane Library databases. This search yielded 151 articles that were reviewed for relevancy, of which 27 were deemed to have met the inclusion criteria for this assessment. The data from these articles were abstracted and the articles were rated for strength of evidence by the panel methodologist.
All 27 studies were rated level III, and a total of 197 SLNBs were reported. Diagnoses included conjunctival and eyelid cutaneous melanoma (85 and 42 patients, respectively), sebaceous gland carcinoma (35 patients), squamous cell carcinoma (26 patients), Merkel cell carcinoma (6 patients), pigmented epithelioid melanocytoid tumor (1 patient), mucoepidermoid carcinoma (1 patient), and signet ring carcinoma (1 patient). Tracer was found in regional lymph nodes in 100% of patients in 21 of 27 articles and in 191 of 197 patients overall. The number of lymph nodes removed ranged from 1 to 16, with most ranging from 1 to 5. Tumor-positive lymph nodes were found in 33 of 197 patients (16.8%), prompting recommendations for adjuvant treatments. Survival data were reported for 16 of these patients, with follow-up periods ranging from 3 to 36 months (average, 12.7 months). Fourteen of 16 patients received adjuvant treatments. Nine were alive and well, 1 was alive with metastases, and 6 had died of metastatic disease (including 2 patients who declined additional treatment). False-negative SLNB results were reported in 5 articles involving 9 of 197 procedures (4.6%). Complications were documented in 7 of 27 articles and included transient facial nerve weakness, persistent blue dye staining of the conjunctiva, neck hematoma, and suture abscess.
Sentinel lymph node biopsy is a promising procedure in patients with eyelid and conjunctival malignancy, and it is useful in identifying sentinel lymph nodes. However, at present, insufficient evidence exists showing that SLNB improves patient outcomes and survival. Recognition of microscopic metastatic disease may prove beneficial in staging and guiding adjuvant therapy.
To determine whether magnetic resonance (MR) imaging with diffusion-weighted (DW) imaging can help discriminate between radiologically indeterminate benign and malignant orbital masses and to ...identify optimal apparent diffusion coefficient (ADC) thresholds for such discrimination.
Informed consent was waived for this HIPAA-compliant institutional review board-approved retrospective study. Forty-seven orbital masses imaged with echo-planar DW imaging were identified in 47 patients (25 female patients, 22 male patients; average age, 35 years). A fellowship-trained orbital surgeon determined reference-standard diagnoses on the basis of chart review, and a neuroradiology fellow and senior neuroradiologist who were blinded to the diagnoses selected a region of interest for each lesion by consensus. ADC was calculated from signal intensity on DW images obtained with b = 1000 and b = 0 sec/mm(2). Lesion ADC was also compared with that of normal-appearing white matter (ADC ratio). The Student t test was used to compare groups. Receiver operating characteristic analysis was performed. Intraobserver agreement was assessed with a repeat data collection.
Malignant lesions had lower ADCs than benign lesions, irrespective of patient age (P < .02) and in adults specifically (P < .05). Lymphomas had lower ADCs than pseudotumors (P < .001). An ADC of less than 1.0 x 10(-3) mm(2)/sec and an ADC ratio of less than 1.2 were optimal for predicting malignancy (sensitivity, 63% for both; specificity, 84% and 90%, respectively; and accuracy, 77% and 81%, respectively). Lymphoma was differentiated from pseudotumor with 100% accuracy (in 16 of 16 cases) by using these values. Infiltrative lesions that were hypointense on T2-weighted images were better characterized with DW imaging than lesions that were hyperintense or well defined.
Echo-planar DW MR imaging can help characterize indeterminate orbital masses.
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