Periocular Tissues Research Articles

Coronavirus disease 2019 (SARS-CoV-2) and colonization of ocular tissues and secretions: a systematic review.

Coronavirus disease 19 (COVID-19) has been described to potentially be complicated by ocular involvement. However, scant information is available regarding severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and ocular structures tropism. We conducted a systematic review of articles referenced in PubMed, Cochrane Library, Web of Science and Chinese Clinical Trial Register (ChiCTR) from December 20, 2019 to April 6, 2020, providing information on the presence of SARS-CoV-2 in cornea, conjunctiva, lacrimal sac, and tears. We excluded ongoing clinical studies as for unobtainable conclusive results. Of 2422 articles, 11 met the inclusion criteria for analysis and were included in the study. None of the studies were multinational. Among the 11 selected papers there were three original articles, one review, four letters, two editorials, and one correspondence letter. Globally, 252 SARS-CoV-2 infected patients were included in our review. The prevalence of ocular conjunctivitis complicating the course of COVID-19 was demonstrated to be as high as 32% in one study only. Globally, three patients had conjunctivitis with a positive tear-PCR, 8 patients had positive tear-PCR in the absence of conjunctivitis, and 14 had conjunctivitis with negative tear-PCR. The majority of the available data regarding SARS-CoV-2 colonization of ocular and periocular tissues and secretions have to be considered controversial. However, it cannot be excluded that SARS-CoV-2 could both infect the eye and the surrounding structures. SARS-CoV-2 may use ocular structure as an additional transmission route, as demonstrated by the COVID-19 patients’ conjunctival secretion and tears positivity to reverse transcriptase-PCR SARS-CoV-2-RNA assay.

Ocular and periocular radiation toxicity in dogs treated for sinonasal tumors: A critical review.

Visual impairment from radiation‐induced damage can be painful, disabling, and reduces the patient's quality of life. Ocular tissue damage can result from the proximity of ocular organs at risk to irradiated sinonasal target volumes. As toxicity depends on the radiation dose delivered to a certain volume, dose‐volume constraints for organs at risk should ideally be known during treatment planning in order to reduce toxicity. Herein, we summarize published ocular toxicity data of dogs irradiated for sinonasal tumors from 36 publications (1976‐2018). In particular, we tried to extract a dose guideline for a clinically acceptable rate of ocular toxicity. The side effects to ocular and periocular tissues were reported in 26/36 studies (72%) and graded according to scoring systems (10/26; 39%). With most scoring systems, however, toxicities of different ocular and periocular tissues are summed into one score. Further, the scores were mostly applied in retrospect and lack volume‐ and dose‐data. This incomplete information reflects the crux of the matter for radiation dose tolerance in canine ocular tissues: The published information of the last three decades does not allow formulating dose‐volume guidelines. As a start, we can only state that a mean dose of 39 Gy (given in 10 x 4.2 Gy fractions) will lead to loss of vision by one or both eyes, while mean doses of <30 Gy seem to preserve functionality. With a future goal to define tolerated doses and volumes of ocular and periocular tissues at risk, we propose the use of combined ocular toxicity scoring systems.

Eyelid Complications Associated with Surgery for Periocular Cutaneous Malignancies.

Periocular skin is highly prone to malignancies, especially basal cell and squamous cell carcinomas. Because of the complex anatomy and eye-protecting functions of the periocular tissues, treatment of these cancers requires special considerations. Mohs micrographic surgery is usually the treatment of choice, whenever possible, in order to enhance margin control while limiting collateral damage to nearby normal structures. Cancer excision, whether by Mohs or other techniques, will leave a complex defect that requires careful anatomical and functional reconstruction. This study presents some of the challenges of treating periocular skin cancer and associated reconstructive surgery and provides an intellectual framework for addressing these challenges. The key topics are adherence to anatomical landmarks and aesthetic units, proper distribution of tension, and matching the correct reconstructive approach, that is, type of flap or graft, to the defect at hand. This review is not meant to be exhaustive, but it will provide both basic and advanced considerations.

Eye Shielding During Head CT Scans: Dose Reduction and Image Quality Evaluation

In this study, we assessed the radiation dose to the lens and the impacts of various eye shields using either a fixed or modulated tube current. Patients undergoing head computed tomography (CT) examinations were recruited, and each was randomly assigned to one of five imaging groups, either without a CT eye shield or with one of two types of shielding and topogram-based tube current modulation (TCM). The radiation dose at the eye lens was estimated using Gafchromic films. All CT images were analyzed for quality in the orbit and brain areas. Two radiologists also qualitatively assessed image artifacts and their impacts on image quality using three-point Likert scales. Both barium sulfate and bismuth-antimony shields significantly reduced radiation dose to the lens (by 28.60%-31.92% and 43.87%-47.00%, respectively) while significantly inducing image artifacts. The image quality of the intraocular structure, but not the intracranial structure, was significantly degraded by shielding. In addition, discriminating the periocular tissues was improved using a bismuth-antimony shield and topogram-based TCM. Compared to fixed tube current, topogram-based TCM provided better signal-to-noise and contrast-to-noise ratios in the intracranial structures when the bismuth-antimony and barium sulfate shields were applied, respectively. Artifacts resulting from the application of eye shields during head CT examinations can be reduced by using topogram-based TCM instead of a fixed tube current. This could be an alternative approach for maintaining image quality in CT scans that do not encompass organ-based TCM.

Vaginal Squamous Cell Carcinoma in a Nelore cow

Background: Skin tumors are the most common neoplasia in veterinary medicine and squamous cell carcinoma (SCC) is the most frequent. In cattle, it is the main tumor besides linfosarcoma and normally affects taurine cattle, but is rare in Nelore cattle. SCC mainly affects mucocutaneous junctions such as the eyelids, sclera, vulva, and perineum, and has already been described in vaginal, eye, and periocular tissues, in addition to the superior digestive tract. The purpose of this paper is to describe a vaginal squamous cell carcinoma in a Nelore cow.Case: A 10-year-old Nelore cow, used as an embryo donor, was submitted to a necropsy procedure. Clinically, the animal had prolonged recumbency, anorexia, weight loss, and vaginal discharge. There was a history of recurrent vaginal prolapses and an intraluminal vaginal mass that had grown over two years. At necropsy, there was diffuse fibrinous peritonitis with marked intestinal adhesions; the vagina was markedly expanded and measured 40 × 20 cm due to the presence of an intraluminal mass occupying the vestibulum and extending up to the cervix. In the vaginal lumen, there was large amount of fibrinonecrotizing malodorous material; the vaginal wall was thickened by an unencapsulated and poorly delimited, firm and white mass composed of sheets and nests of epithelial cells from the squamous layer surrounded by abundant fibrovascular stroma. The neoplastic cells were polygonal with marked pleomorphism, anisokariosis, and anisocytosis; abundant; eosinophilic; and had well-defined cytoplasmic borders. Sometimes it was possible to see desmosomes. The nuclei were rounded to oval with sparse chromatin and one or more nucleoli were seen. Mitotic figures were frequent (at least 3 per higher power field) and there were also a few multinucleated cells. Frequently, there was the formation of distinct keratin “pearls”.Discussion: SCC frequently occurs in the skin, eyes, and vulva in cattle, since these are sites that lack pigment within the epidermis and have prolonged exposed to ultraviolet light. Vaginal SCC has already been described in one cow with recurrent vaginal prolapses that was submitted to follicular aspiration. In a survey of cattle tumors, most genital tract neoplasias affected the uterus, and vaginal tumors normally originated from connective tissue - fibromas, fibropapillomas, and fibrosarcoma - or muscular tissue - leiomyoma and leiomyosarcoma. Irreversible changes in cellular DNA can occur due to physical or chemical carcinogens, and also chronic inflammation. The cow in this paper was frequently submitted to follicular aspiration and this can cause chronic inflammation in the vaginal mucosa after the puncture and, when it’s chronic, can represent one of the main initiating factors for tumor development. This cow’s death was caused by diffuse and marked peritonitis. The same cause was previously described in cows submitted to follicular aspiration and, in one of these animals, there was a rectal perforation caused by mistakes during the procedure. In this animal, we did not find any lesions in the rectum or intestines, however, considering the gravity of the peritonitis, we were not able to exclude this hypothesis. Papillomavirus has previously been found in SCC in sheep and probably acts synergistically with ultraviolet light, however, in this animal, we did not test for the virus. Squamous cell carcinoma in an uncommon tumor in cows’ vaginas, however, this should be included as a possible differential diagnosis, especially in animals submitted to situations that can cause chronic inflammation in the genital tract.

Periocular Sebaceous Carcinoma Masquerading as an Intratarsal Cyst.

A 60-year-old woman with no significant medical history presented to an outside eye care provider for a persistent right lower eyelid lesion. This lesion was diagnosed as a chalazion, and she underwent incision and drainage. Postoperatively, the lesion did not resolve and maintained the same size and appearance. She was referred 6 months later for tarsal cyst excision. Examination was remarkable for an intratarsal cystic lesion involving the margin of the right lower eyelid (Fig. A, B). There was no associated madarosis, ulceration, bleeding, keratinization, or telangiectasia. A wedge excision and reconstruction were performed. Pathologic examination revealed a poorly differentiated sebaceous carcinoma (Fig. C, D). The patient underwent a second resection and conjunctival map biopsies, which showed negative surgical margins and no conjunctival involvement. She subsequently underwent reconstruction, and there was no evidence of recurrence at 6-month follow-up.External photograph demonstrating a right lower eyelid sebaceous cell carcinoma and corresponding histological findings. A,B, The cystic lesion involves the posterior aspect of the tarsus and extends to the margin. C, Lower power photomicrograph demonstrating the cystic growth pattern of the lesion (hematoxylin and eosin; original magnification = ×10). D, High magnification photomicrograph demonstrating that the cyst wall is composed of atypical cells with marked nuclear pleomorphism and vacuolated or foamy cytoplasm in many cells (hematoxylin and eosin; original magnification = ×300).Sebaceous carcinoma is a relatively rare, aggressive malignancy most commonly arising from the periocular tissues including the meibomian glands of the tarsus, and the glands of Zeis of the eyelashes, caruncle, and skin of the eyebrow. Although sebaceous carcinoma accounts for only 0.5% of all eyelid lesions, it is the most concerning because it is associated with increased morbidity and mortality. This periocular malignancy is notoriously difficult to diagnose, masquerading as an assortment of conditions which frequently leads to delays in diagnosis and proper treatment in greater than two thirds of cases. Despite a seemingly benign appearance, any lesion with yellow coloration and thickening of the eyelid or adjacent conjunctiva should cause the clinician to consider sebaceous carcinoma as a possibility with a low threshold for biopsy.

Immunohistochemical Detection of Encephalitozoon cuniculi in Ocular Structures of Immunocompetent Rabbits.

Simple SummaryEncephalitozoonosis is a common infectious disease widely spread among rabbits. Its causative agent, Encephalitozoon cuniculi, is considered to be transmissible to humans. In rabbits, clinical signs include discoordination, head tilt, excessive water intake, excessive urination and cataracts. This study investigates, for the first time, whether the E. cuniculi organism can be detected in ocular structures in healthy adult rabbits after experimental oral infection using immunohistochemistry—detection of the organism in the tissue using a specific staining method. In infected animals, E. cuniculi spores were detected in many ophthalmic structures (periocular connective tissue, sclera, cornea, choroidea, iris, retina and lens) as early as 2 weeks after infection. There were no signs of inflammatory lesions in any of the ocular tissues examined at 2, 4, 6 and 8 weeks after infection. E. cuniculi was also detected in the lens of adult rabbits, which indicates that ways of lens infection other than intrauterine and haematogenic are possible. This information can help to understand E. cuniculi dissemination to various ocular tissues structures after oral infection.Encephalitozoonosis is a common infectious disease widely spread among rabbits. Its causative agent, Encephalitozoon cuniculi, is considered as a zoonotic and emerging pathogen capable of infecting both immunocompetent and immunocompromised hosts, including humans. In rabbits, clinical signs include neurological, kidney and ocular disease. The aim of this study was to detect E. cuniculi in ocular structures in immunocompetent rabbits after experimental oral infection using immunohistochemistry. In infected animals, E. cuniculi spores were present in periocular connective tissue, sclera, cornea, choroidea, iris, retina and lens, as a round to ovoid organism reacting with a specific anti-E. cuniculi monoclonal antibody as early as 2 weeks after infection. There were no signs of inflammatory lesions in any of the ocular tissues examined at 2, 4, 6 and 8 weeks after infection. In the present study, E. cuniculi was also detected in the lenses of adult rabbits, which indicates that ways of lens infection other than intrauterine and haematogenic are possible.

Immunological Aspects of Graves' Ophthalmopathy.

The body's autoimmune process is involved in the development of Graves' disease (GD), which is manifested by an overactive thyroid gland. In some patients, autoreactive inflammatory reactions contribute to the development of symptoms such as thyroid ophthalmopathy, and the subsequent signs and symptoms are derived from the expansion of orbital adipose tissue and edema of extraocular muscles within the orbit. The autoimmune process, production of antibodies against self-antigens such as TSH receptor (TSHR) and IGF-1 receptor (IGF-1R), inflammatory infiltration, and accumulation of glycosaminoglycans (GAG) lead to edematous-infiltrative changes in periocular tissues. As a consequence, edema exophthalmos develops. Orbital fibroblasts seem to play a crucial role in orbital inflammation, tissue expansion, remodeling, and fibrosis because of their proliferative activity as well as their capacity to differentiate into adipocytes and myofibroblasts and production of GAG. In this paper, based on the available medical literature, the immunological mechanism of GO pathogenesis has been summarized. Particular attention was paid to the role of orbital fibroblasts and putative autoantigens. A deeper understanding of the pathomechanism of the disease and the involvement of immunological processes may give rise to the introduction of new, effective, and safe methods of treatment or monitoring of the disease activity.

The Flip-Back Myocutaneous Advancement Flap for Periocular Reconstruction.

To present a novel myocutaneous flap for anterior lamellar reconstruction. Retrospective interventional case series of consecutive patients who underwent Mohs reconstruction using the flip-back flap. Operations were performed by a single surgeon (DTT) between January 2012 and May 2016. For lower eyelid defects, an extended subciliary incision was made and a skin-muscle flap developed and suspended in the manner of lower eyelid blepharoplasty. A back-cut was used to develop a pedicle from the overlapping tissue, which was then rotated 180 degrees into the defect. A similar method was employed in an inverted manner for upper eyelid defects. Postoperative eyelid function, cosmesis, complications, and need for further interventions were assessed. Ten patients-8 with lower and 2 with upper eyelid defects-were reconstructed using this method. Mean follow up was 18.3 ± 15.5 months with a minimum interval of 4 months. Despite the 180-degree rotation of a relatively narrow pedicle, none of the patients experienced flap necrosis. Postoperative function and cosmesis was satisfactory, with no tissue puckering, notching, or symptomatic retraction. No antimetabolite/steroid injection or surgical revision was required. The flip-back flap expands the armamentarium of the periocular reconstructive surgeon. Its particular forte is in addressing broad and relatively shallow anterior lamellar defects where sufficient tissues are not available for transposition via a uni- or bipedicle flap. By leveraging the robust periocular vascular plexus and defying traditional guidelines governing pedicle formation and rotation, it permits creation of a local flap in cases where skin grafts or extensive Mustarde-style flaps might otherwise be required.The flip-back myocutaneous flap offers a novel alternative to skin grafting or more extensive cheek rotational flaps for reconstruction of challenging anterior lamellar defects involving the eyelids and adjacent periocular tissues.

Effect of aging in periocular appearances by comparison of anthropometry between early and middle adulthoods in Chinese Han population

Age-related change in ocular appearance occurs throughout adulthood, and involutional alterations in periocular tissues are common in middle-aged or older adults. This study sought to investigate significant differences in periocular anthropometry between young and middle-aged adults of Chinese Han ethnic group. A total of 589 Chinese Han adults were recruited for cross-sectional investigation: 309 young adults (20 to 30 years), and 280 middle adulthood (50 to 70 years). Standardized, frontal view photographs were taken from each subject for measurements of 17 ocular anthropometric parameters (11 linear, three angular and three indicial parameters) detailing dimensions of palpebral fissures, and eyebrows. Eyelid crease morphologies were also evaluated. Distribution of eyelid crease subtypes were different between the two age-groups, and an eyelid subtype (Type VI Closed Crescent) was uniquely found in middle-aged adults. Significant differences were found in majority of the ocular parameters. For most of the fissure-related measurements, values were greater in young adults. For some distance-dimensions between eyes and eyebrows, values were greater in the middle-aged adults. Detailed evaluation of periocular parameters of different age was individually performed for two subjects, which embodied findings from the cross-sectional analysis. By comparison of anthropometries between age-groups, we found alterations in periocular and eyelid morphologies under effect of aging, with association of laxity and loss of elasticity in periocular tissues. This study was the first to provide normative periocular dimensions of early and middle adulthoods in Chinese Han, which is useful for considerations in esthetic surgical decision-making for this population.

Pathological ASXL1 Mutations and Protein Variants Impair Neural Crest Development.

SummaryThe neural crest (NC) gives rise to a multitude of fetal tissues, and its misregulation is implicated in congenital malformations. Here, we investigated molecular mechanisms pertaining to NC-related symptoms in Bohring-Opitz syndrome (BOS), a developmental disorder linked to mutations in the Polycomb group factor Additional sex combs-like 1 (ASXL1). Genetically edited human pluripotent stem cell lines that were differentiated to NC progenitors and then xenotransplanted into chicken embryos demonstrated an impairment of NC delamination and emigration. Molecular analysis showed that ASXL1 mutations correlated with reduced activation of the transcription factor ZIC1 and the NC gene regulatory network. These findings were supported by differentiation experiments using BOS patient-derived induced pluripotent stem cell lines. Expression of truncated ASXL1 isoforms (amino acids 1–900) recapitulated the NC phenotypes in vitro and in ovo, raising the possibility that truncated ASXL1 variants contribute to BOS pathology. Collectively, we expand the understanding of truncated ASXL1 in BOS and in the human NC.

Soft Tissue Metrics in Thyroid Eye Disease: An International Thyroid Eye Disease Society Reliability Study

To determine the reliability of 3 scales for assessing soft tissue inflammatory and congestive signs associated with thyroid eye disease. This was a multicentered prospective observational study, recruiting 55 adults with thyroid eye disease from 9 international centers. Six thyroid eye disease soft tissue features were measured; each sign graded using 3 scales (presence/absence [0-1], 3-point scale [0-2], and percentage [0-100]). Each eye was graded twice by 2 independent raters. Accuracy (fraction of agreement) was calculated between the 2 trials for each rater (intrarater reliability) and between raters for all trials (interrater reliability) to determine the most sensitive scale for each feature that maintained a threshold of agreement greater than 0.70. Trial, intrarater reliability, and interrater reliability were determined by accuracy measurement of agreement for each inflammatory/congestive feature. Fifty-five patients had 218 assessments for 6 thyroid eye disease metrics. The intrarater reliability for each feature was consistently better than the interrater reliabilities. Using an agreement of 0.70 or better, for the interrater tests, conjunctival and eyelid edema could be reliably measured using the 0-1 or 0-2 scale while conjunctival and eyelid redness could only be reliably measured with the binary 0-1 scale. Caruncular edema and superior conjunctival redness could not be measured reliably between 2 raters with any scale. The percentage scale had poor agreement unless slippage intervals of >20% were allowed on either side of the measurements. Of the specific periocular soft tissue inflammatory features measured between raters in the Clinical Activity Score and Vision, Inflammation, Strabismus, Appearance scales, edema of the eyelids and conjunctiva could reliably be measured by both 0-1 and 0-2 scales, erythema of the eyelid and bulbar conjunctiva could reliably be measured only by the 0-1 scale, and the other parameters of superior bulbar erythema and caruncular edema were not reliably measured by any scale.

HIF2A-LOX Pathway Promotes Fibrotic Tissue Remodeling in Thyroid-Associated Orbitopathy.

Thyroid-associated orbitopathy (TAO) is a disfiguring periocular connective tissue disease associated with autoimmune thyroid disorders. It is a potentially blinding condition, for which no effective pharmacological treatment has been established. Despite a suggested role played by autoimmune thyrotropin receptor activation in the pathogenesis of TAO, the cellular and molecular events contributing to the fibrotic and inflammatory disease process of TAO are not fully defined. By developing a three-dimensional organoid culture of human orbital fibroblasts (OFs), we sought to determine the molecular mechanism underlying the fibrotic disease process of TAO. In this ex vivo model, we have demonstrated that hypoxia-inducible factor (HIF) 2α (HIF2A), but not its paralog HIF1A, accelerates extracellular matrix (ECM) deposition by inducing a collagen-cross-linking enzyme, lysyl oxidase (LOX). Inhibiting HIF2A and LOX with short hairpin RNA or small molecular antagonists effectively ameliorated fibrotic disease process within TAO organoids. Conversely, the overexpression of a constitutively active HIF2A in mouse OFs was sufficient to initiate LOX-dependent fibrotic tissue remodeling in OF organoids. Consistent with these findings, HIF2A and LOX were highly expressed in human TAO tissues paralleling excess ECM deposition. We propose that the HIF2A-LOX pathway can be a potential therapeutic target for the prevention and treatment of TAO.

Cell survival controlled by lens-derived Sema3A-Nrp1 is vital on caffeine-suppressed corneal innervation during chick organogenesis.

In this study, we investigated the effect of caffeine overexposure on corneal innervation in the early chicken embryo. Caffeine administration restricted corneal innervation by affecting trigeminal nerve development. Immunohistochemistry for phospho-Histone3 (pHIS3) and C-caspase3 revealed that cell survival was repressed by caffeine administration. Whole-mount in situ hybridization against semaphorin 3A (Sema3A) and neuropilin-1 (Nrp1) showed that both caffeine and 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AAPH, a free radical generator) administration upregulates the expression of both Sema3A and Nrp1. Next, we demonstrated that lens ablation in the developing chicken embryos significantly affected NF-labeled periocular nerve fascicles and innervation to the central eye region. Subsequently, we used a neuroblastoma cell line to investigate in vitro whether or not Sema3A-Nrp1 signaling exerts a key role on the caffeine-suppressed neuron survival. Knocking-down Sema3A through transfection with Sema3A-siRNA dramatically decreased the responsiveness of cells to caffeine administration, as well as cell apoptosis. We suggest that Sema3A-Nrp1 signaling regulates Trp53 and Cdkn1a through Slit2-Robo1 and Ephb2. Taken together, we speculate here that caffeine-enhanced reactive oxygen species upregulates Sema3A-Nrp1 expression in the lens and periocular tissues, resulting in corneal cell apoptosis, accompanied by its chemorepellent role on the invasion of the developing cornea by trigeminal sensory fibers.

Tear Film Stability in Patients with Pseudexfoliation

Abstract Pseudoexfoliation syndrome is an age related disorder, characterized by abnormal fibrous fiber production and accumulation in different visceral organs as well as in the eye and periocular tissues. Hystological examination recorded the presence of the pseudoexfoliation in the conjunctiva, and they can disturb the accessory lacrimal gland and goblet cell function. This can explain tear film instability in patients with pseudoexfoliations. In our study, we examined the tear film stability in patients with and without pseudoexfoliation, using Schirmer test and tear break up time test. Our results indicated that patients with pseudoexfoliation had lower values of Schirmer and tear break up time tests than patients without it. Pseudoexfoliation is the main reason for the instability of the tear film, because of its negative impact on the conjucntival goblet cells. In conclusion, ophthalmologists must have these data on their mind in the process of the pseudoexfoliation glaucoma treatment and controlling.

Use of an ocular wound chamber for the prevention of exposure keratopathy in a guinea pig model.

Current therapies available to treat and heal ocular surface injuries and periocular burns are frequently inadequate, costly, and labor intensive. To address these limitations, we have employed a flexible, semitransparent ocular wound chamber (OWC) to provide protection as well as a watertight seal to allow for the constant delivery of therapeutics to the ocular surface and surrounding periocular tissue. This study demonstrates the safety and utilization of the OWC on uninjured eyes and in our exposure keratopathy model. For initial safety studies (N = 3 per group), the eyelids remained intact and the eye uninjured. A blepharotomy (N = 6 per group) was performed to remove the upper and lower eyelids surrounding the left (OS) eye to create our exposure keratopathy model. Right (OD) eyes served as uninjured controls in all studies. Following OWC placement, 0.5 mL HPMC gel or balanced saline solution (BSS) was injected into the chamber. Animals were monitored daily and fully assessed via white light, fluorescein, and OCT imaging at least through 72 hours post OWC placement. In studies that included a blepharotomy, skin samples were analyzed by multiplex cytokine analysis. Results of safety experiments revealed no significant differences between treatment groups in corneal thickness, fluorescein staining, OCT imaging, or histological eye or skin sections when compared to control eyes. In our exposure keratopathy model, OWC treated eyes showed significantly less fluorescein uptake and also were found to have significantly lower levels of cytokines IL-13 and IL-5 in skin samples. These results demonstrate for the first time that treatment using the OWC device is not only safe, but significantly protects against blepharotomy-induced exposure keratopathy. As a whole, this study advances our overall efforts to develop a feasible solution to treat ocular surface injuries, infections, and periocular burns.

Serotype survey of AAV gene delivery via subconjunctival injection in mice.

AAV gene therapy approaches in the posterior eye resulted in the first FDA-approved gene therapy-based drug. However, application of AAV vectorology to the anterior eye has yet to enter even a Phase I trial. Furthermore, the simple and safe subconjunctival injection has been relatively unexplored in regard to AAV vector transduction. To determine the utility of this route for the treatment of various ocular disorders, a survey of gene delivery via natural AAV serotypes was performed and correlated to reported cellular attachment factors. AAV serotypes packaged with a self-complementary reporter were administered via subconjunctival injection to WT mice. Subconjunctival injection of AAV vectors was without incidence; however, vector shedding in tears was noted weeks following administration. AAV transduction was serotype dependent in anterior segment tissues including the eye lid, conjunctiva, and cornea, as well as the periocular tissues including muscle. Transgene product in the cornea was highest for AAV6 and AAV8, however, their corneal restriction was remarkably different; AAV6 appeared restricted to the endothelium layer while AAV8 efficiently transduced the stromal layer. Reported AAV cellular receptors were not well correlated to vector transduction; although, in some cases they were conserved among mouse and human ocular tissues. Subconjunctival administration of particular AAV serotypes may be a simple and safe targeted gene delivery route for ocular surface, muscular, corneal, and optic nerve diseases.

In Vivo Effects of Retrobulbar Bimatoprost Injection on Orbital Fat.

Recent publications have reported the adverse effects of prostaglandin analogues on the periocular tissues. These medications may cause periorbital lipodystrophy, enophthalmos, and deepening of the superior sulcus deformity. While these effects may have adverse consequences for some patients, the atrophy of the periorbital fat may have a useful role in diseases that lead to orbital and periorbital fat hypertrophy such as thyroid eye disease. In this pilot study, the authors investigated the effects of retrobulbar bimatoprost injection on the intraocular pressure and orbital fat in a rat animal model. Three rats were sedated and intraocular pressure was measured. A 0.1 ml aliquot of bimatoprost was injected into the right orbit of all rats. In the left orbit, 0.1 ml of phosphate-buffered saline was injected as a control. Three weeks later, all rats were sedated and intraocular pressure was measured before euthanizing. Routine histologic staining was performed and thin sections through the intraconal orbital fat were obtained. Density of intraconal adipocytes was measured and adipocyte heterogeneity was determined using a computer image analysis algorithm. The specimens injected with bimatoprost demonstrated atrophy of orbital fat with significantly increased adipocyte density (p = 0.009) and heterogeneity (p = 0.008) when compared with control. Intraocular pressure was not significantly decreased at 3 weeks after injection of retrobulbar bimatoprost. In this pilot study, orbital injection of bimatoprost demonstrated atrophy of intraconal adipocytes when compared with control orbits injected with saline. The orbits injected with bimatoprost were noted to have smaller, more heterogeneous adipocytes that were densely packed in the intraconal space. The study limitations include the small sample size, which limited the ability for us to make conclusions about the effect on intraocular pressure. Nevertheless, the findings presented suggest that retrobulbar bimatoprost may present a nonsurgical alternative to induce atrophy of the orbital fat without inducing inflammation or hypotony.

The utilization of an ocular wound chamber on corneal epithelial wounds

PurposeCurrently available ocular moisture chambers are not adequate to manage the treatment of periocular burns, corneal injuries, and infection. The purpose of these studies was to demonstrate that a flexible, semi-transparent ocular wound chamber device adapted from technology currently used on dermal wounds is safe for use on corneal epithelial injuries.Materials and methodsA depilatory cream (Nair™, 30 seconds) was utilized to remove the excess hair surrounding the left eyes of anesthetized Institute Armand Frappier (IAF) hairless, female guinea pigs (Crl:HA-Hrhr). A 4 mm corneal epithelium defect was created using a corneal rust ring remover (Algerbrush®II). Epithelial defects were either left untreated or the eyes were fitted with an ocular wound chamber and 0.5 mL of hydroxypropyl methylcellulose (HPMC) gel (GenTeal®) or HPMC liquid (GenTeal®) was injected into each chamber (N=5 per group). At 0, 24, 48, and 72 hours fluorescein and optical coherence tomography imaging was collected and the intraocular pressure (IOP) was measured. H&E staining was performed on corneal and eyelid skin samples and evaluated by a veterinary pathologist.ResultsCorneal epithelial wounds demonstrated 100% closure rates when left untreated or treated with an ocular wound chamber containing HPMC gel at 72 hours while wounds treated with an ocular wound chamber containing HPMC liquid were 98% healed. No significant differences were found in corneal thickness and wound healing, IOP, or eyelid skin pathology in any treatment group when compared to controls.ConclusionsThis study indicates that adapted wound chamber technology can be safely used on sterile, corneal epithelial wounds without adverse effects on periocular or ocular tissue when filled with a liquid or gel.

Case series: periocular habronemiasis in five horses in the Netherlands

In tropical and subtropical climates, infection of periocular tissue by Habronema larvae is a recognised cause of conjunctivitis or blepharitis. To the authors’ knowledge, only a few cases of habronemiasis...