Epithelial-mesenchymal transition (EMT) and endothelial-mesenchymal transition (EndMT) are physiological processes required for normal embryogenesis. However, these processes can be hijacked in pathological conditions to facilitate tissue fibrosis and cancer metastasis. In the eye, EMT and EndMT play key roles in the pathogenesis of subretinal fibrosis, the end-stage of age-related macular degeneration (AMD) that leads to profound and permanent vision loss. Predominant in subretinal fibrotic lesions are matrix-producing mesenchymal cells believed to originate from the retinal pigment epithelium (RPE) and/or choroidal endothelial cells (CECs) through EMT and EndMT, respectively. Recent evidence suggests that EMT of RPE may also be implicated during the early stages of AMD. Transforming growth factor-beta (TGFβ) is a key cytokine orchestrating both EMT and EndMT. Investigations in the molecular mechanisms underpinning EMT and EndMT in AMD have implicated a myriad of contributing factors including signaling pathways, extracellular matrix remodelling, oxidative stress, inflammation, autophagy, metabolism and mitochondrial dysfunction. Questions arise as to differences in the mesenchymal cells derived from these two processes and their distinct mechanistic contributions to the pathogenesis of AMD. Detailed discussion on the AMD microenvironment highlights the synergistic interactions between RPE and CECs that may augment the EMT and EndMT processes in vivo. Understanding the differential regulatory networks of EMT and EndMT and their contributions to both the dry and wet forms of AMD can aid the development of therapeutic strategies targeting both RPE and CECs to potentially reverse the aberrant cellular transdifferentiation processes, regenerate the retina and thus restore vision.
AIM: To demonstrate prognostic factors for poor visual outcome in patients with post-traumatic endophthalmitis (PTE) following open globe injury. METHODS: A retrospective study was conducted on 66 patients (66 eyes) with PTE following open globe injury from 2005 to 2015. Potential factors accounting for good and poor visual outcome were statistically analyzed by Chi-square test and Logistic regression model. RESULTS: In 66 cases, 39 cases (59%) had a poor visual outcome. Univariate and multivariate Logistic regression analysis identified retained intraocular foreign body (IOFB) as the only factor significantly associated with poor visual outcome [adjusted odds ratio, 4.62; 95% confidence interval (1.04-20.53); =0.04]. The most common causative agents were gram-positive organisms (83%), of which (33%), was the most common pathogen. All cases received intravitreal antibiotic injections. Oral ciprofloxacin was the most used systemic antibiotic (33%). Pars plana vitrectomy was performed in 83% (55/66) of cases. At 6mo follow-up, mean BCVA was 1.74±0.72 logMAR units. CONCLUSION: In patients with PTE following open globe injury, the only predictor of poor visual outcome is the presence of IOFB. is the most isolated microorganism.
PURPOSE: To report the novel application of nontreponemal and treponemal antibody to confirm diagnosis of ocular syphilis from vitreous samples. METHODS: Two distinct case reports emphasizing the importance of confirmatory vitreous treponemal antibody. Multimodal imaging of patients was also applied. RESULTS: We report two distinct cases with positive serum treponemal antibody but opposing vitreous treponemal antibody results. One case with a positive vitreous test responded well to antisyphilitic treatment. By contrast, a case with a negative vitreous result was changed to serpiginous choroiditis, eventually cured by immunomodulatory treatment. CONCLUSION: Intraocular fluid analysis of nontreponemal and treponemal antibody may play an important role in ruling out suspected ocular syphilis in settings without a polymerase chain reaction facility, especially immunocompromised patients who are at risk of multiple infections. Further studies are needed to establish the sensitivity and specificity of nontreponemal and treponemal antibody test on vitreous samples.
PURPOSE: To quantitatively analyze the angle anatomy in eyes with a Boston type 1 keratoprosthesis (KPro) using anterior segment optical coherence tomography (AS-OCT) and to assess the diagnostic ability of AS-OCT in KPro-associated glaucoma. METHODS: AS-OCT (RTVue) images from KPro eyes with and without glaucoma were reviewed. The angle opening distance at 500 μm from the scleral spur (AOD500), trabecular-iris angle at 500 μm from the scleral spur (TIA500), and trabecular-iris surface area at 500 μm from the scleral spur (TISA500) were measured by 2 observers masked to the diagnosis. The measurements for each visible quadrant were compared between KPro eyes with and without glaucoma. RESULTS: Twenty-two eyes with glaucoma and 17 eyes without glaucoma from 39 patients with KPro were included. Of the 4 quadrants imaged, the temporal angle was the most visible (79.5%) and angle measurements of the temporal quadrant were the only ones that differentiated the 2 groups: the mean AOD500, TIA500, and TISA500 were significantly lower in KPro eyes with glaucoma than without glaucoma (388.2 ± 234.4 μm vs. 624.5 ± 310.5 μm, P = 0.02; 26.1 ± 14.0 degrees vs. 39.1 ± 17.1 degrees, P = 0.03; and 0.15 ± 0.09 mm vs. 0.23 ± 0.12 mm, P = 0.03; respectively). The highest area under the receiver operating characteristic curve for detecting glaucoma was 0.75 for temporal TIA500 (95% confidence interval 0.57-0.94, P = 0.02) with 50% specificity at 80% of sensitivity and a cutoff value of 37 degrees. CONCLUSIONS: The temporal angle was the most visible on AS-OCT in eyes with a KPro. Significant narrowing of the temporal angle detected on AS-OCT was associated with glaucoma in these eyes.
BACKGROUND: Postoperative radioactive iodine (RAI) administration is widely utilized in patients with differentiated thyroid cancer. While beneficial in select patients, it is critical to recognize the potential negative sequelae of this treatment. The prevention, diagnosis, and management of the salivary and lacrimal complications of RAI exposure are addressed in this consensus statement. METHODS: A multidisciplinary panel of experts was convened under the auspices of the American Head and Neck Society Endocrine Surgery and Salivary Gland Sections. Following a comprehensive literature review to assess the current best evidence, this group developed six relevant consensus recommendations. RESULTS: Consensus recommendations on RAI were made in the areas of patient assessment, optimal utilization, complication prevention, and complication management. CONCLUSION: Salivary and lacrimal complications secondary to RAI exposure are common and need to be weighed when considering its use. The recommendations included in this statement provide direction for approaches to minimize and manage these complications.
The delivery of ophthalmic drugs is challenging despite easy accessibility via the ocular surface. Topical instillation of eye drops is a relatively easy and most commonly used as a conduit for drug delivery for treating a myriad of ocular morbidities, particularly involving the anterior segment, and has an additional benefit of avoiding the first-pass metabolism while passing through the systemic circulation. The primary challenges of drug administration through traditional methods include-inadequate patient education for proper drug instillation technique, compliance, adherence, and persistence. Various dynamic (choroidal and conjunctival blood flow, lymphatic clearance, and tear dilution) and static (namely, different layers of cornea, sclera, and retina including blood aqueous and blood-retinal barriers) ocular barriers limit drug delivery to the target ocular tissues. The maintenance of the therapeutic drug levels on the ocular surface for a prolonged duration is an added challenge, thus preventing persistent delivery for longer durations. These factors result in inadequate management, leading to poor prognosis in vision loss in as many as 27% of the patients diagnosed with glaucoma. We have reviewed the research and advancements in the development of novel and well-tolerated drug delivery systems with the common goal of overcoming the factors limiting adequate drug delivery to the target tissues in glaucomatous patients with traditional techniques. In the recent past, multiple research groups have successfully designed noninvasive, sustained drug delivery systems, promoting the efficacy as well as the feasibility of delivering topical drugs to the anterior segment.
PURPOSE: Report the efficacy of cyanoacrylate tissue adhesive (CTA) application in the management of corneal thinning and perforations associated with microbial keratitis. METHODS: A retrospective review of consecutive patients who underwent CTA application for corneal thinning and perforation secondary to microbiologically proven infectious keratitis between 2001 and 2018 at a single center. We defined successful CTA application as an intact globe without tectonic surgical intervention. RESULTS: The cohort included 67 patients, and 37 presented with corneal perforation while 30 had corneal thinning. The perforation/thinning was central/paracentral in 43 eyes and peripheral in 23 eyes. The underlying infectious etiologies were monomicrobial in 42 cases (35 bacterial, 3 fungal, 2 viral, and 2 acanthamoeba cases) and polymicrobial in 25 cases (22 polybacterial cases and 3 cases with a combination of Gram positive bacteria and fungus). The median duration of glue retention was 29 days. The CTA success rate was 73%, 64%, and 44% at 10, 30, and 180 days, respectively. CTA application appears more successful in monomicrobial (vs. polymicrobial) and Gram positive bacterial (vs. Gram negative) keratitis but the differences are statistically non-significant. The location of perforation/thinning and the use of topical corticosteroid were not associated with CTA failure. CONCLUSION: CTA was moderately effective in restoring globe integrity in severe corneal thinning and perforation secondary to microbial keratitis in the short term. However the majority of patients require tectonic surgical intervention within 6 months. CTA application success is not significantly associated with the location of thinning/perforation or the use of topical corticosteroid.
The current evidence suggests that masks are efficacious in limiting the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). Although cloth masks are effective in outdoor environments, there is a consensus about the requirement of N95 masks or respirators when working in close proximity to patients who may be asymptomatic carriers, specifically in ophthalmology clinics, where slit-lamp examinations, noncontact tonometry, and other procedures place the physicians and patients in close proximity with each other. In this report, we review the available evidence regarding the efficacy of different types of masks in clinical practice in ophthalmology.
PURPOSE: To review the current regimens and novel therapeutic modalities in various stages of research and development for the management of non-infectious posterior uveitis (NIPU). METHODS: We performed a thorough review of current literature using PubMed, Google Scholar and Clinicaltrials.gov to identify the published literature about the available therapeutics and novel drugs/therapies in different stages of clinical trials. RESULTS: The current management regimen for non-infectious posterior uveitis includes corticosteroids, immunomodulatory therapies and anti-metabolites. However, NIPU requires long-term management for efficacious remission of the disease and to prevent disease relapse. Long-term safety issues associated with steroids have led to efforts to develop novel therapeutic agents including biological response modulators and immunosuppressants. The current therapeutic agents in various stages of development include calcineurin inhibitors, biologic response modifiers and a more a comprehensive modalities like ocular gene therapy as well as novel drug delivery mechanisms for higher bioavailability to the target tissues, with minimal systemic effects. CONCLUSION: Novel efficacious therapeutic modalities under development will help overcome the challenges associated with the traditional therapeutic agents.
PURPOSE: In this study, we quantify Pigment Epithelium-derived Factor (PEDF) secreted by corneal epithelial cells and evaluate its immunomodulatory functions in a murine model of dry eye disease (DED). METHODS: We induced DED in female C57BL/6 mice using a controlled environment chamber for 14 days. We quantified mRNA expression of Serpinf1 gene and PEDF protein synthesis by corneal epithelial cells (CEpCs) using RT-PCR and ELISA. CEpCs from normal or DED mice were cultured with IFNγ-stimulated-dendritic cells (DCs) for 24 h, and expression of MHC-II and CD86 by DCs was determined using flow cytometry. Next, we either added recombinant PEDF (rPEDF) or anti-PEDF antibody to co-culture, and DC expression of the above maturation markers was quantified. Lastly, we treated DED mice with either topical rPEDF, anti-PEDF Ab or murine serum albumin (MSA), and DC maturation, expression of pro-inflammatory cytokines, and DED severity were investigated. RESULTS: Serpinf1 mRNA expression and PEDF protein production levels by CEpCs were upregulated in DED. CEpCs from DED mice exhibited an enhanced suppressive effect on the expression of MHC-II and CD86 by DCs, compared to normal mice. This effect was abolished by blocking endogenous PEDF with anti-PEDF Ab or enhanced by supplementing with rPEDF. Treatment with anti-PEDF antibody blocked the effect of endogenous-PEDF and increased DC maturation, expression of pro-inflammatory cytokines in conjunctivae, and exacerbated disease severity in DED mice. Conversely, topical rPEDF enhanced the suppressive effect of endogenous PEDF on DC maturation, decreased expression of pro-inflammatory cytokines in conjunctivae, and reduced disease severity. CONCLUSIONS: The results from our study elucidate the role of PEDF in impeding DC maturation, and suppression of ocular surface inflammation, explicating a promising therapeutic potential of PEDF in limiting the corneal epitheliopathy as a consequence of DED.
PURPOSE: To establish the prevalence, clinical characteristics, and risk factors for persistent corneal epithelial defects (PED) in patients with chronic ocular graft-versus-host disease (oGVHD) and to determine visual outcomes after healing. DESIGN: Retrospective cohort study. METHODS: A chart review was conducted of patients in whom chronic oGVHD was diagnosed between January 2011 and December 2018 and their demographic and clinical characteristics were collected. Data were analyzed to determine prevalence of PED, and multivariate logistic regression was performed to determine the risk factors associated with it. RESULTS: A total of 405 patients at a mean age of 60 ± 13 years in whom chronic oGVHD was diagnosed; 58% were men. The prevalence of PED was 8.1%. The median time for PED development after hematopoietic stem cell transplantation was approximately 24 months. Median time to PED resolution was 4.5 weeks after starting therapy. The mean best-corrected visual acuity declined by 2 lines post-PED resolution. The prevalence rates of corneal ulcer and perforation were 6.2% and 4.0%, respectively, over 8 years. Logistic regression analysis, used to determine factors associated with PED, showed diabetes (P = .006), limbal stem cell deficiency (LSCD) (P = .02), filamentary keratitis (P = .02), subconjunctival fibrosis (P = .02), and a higher National Institutes of Health (NIH) oGVHD score (P = .01) were significant risk factors for PED development. CONCLUSIONS: The study found the prevalence rate of PED, corneal ulceration, and corneal perforation in chronic oGVHD to be 8.1%, 6.2%, and 4%, respectively. Analysis showed that oGVHD patients with diabetes, LSCD, filamentary keratitis, subconjunctival fibrosis, and a high NIH score were at higher risk of developing severe corneal disease.
PURPOSE: To determine if female hormonal therapy (FHT) increases the incidence of noninfectious uveitis. DESIGN: Retrospective cohort study. PARTICIPANTS: Women exposed to FHT and matched women unexposed to FHT enrolled in a national insurance plan. METHODS: Estimation of noninfectious uveitis incidence used multivariable Cox proportional hazards regression. To account for differences between the exposed and unexposed cohorts, a propensity score for being prescribed FHT was created using logistic regression, and inverse probability of treatment weighting was performed. MAIN OUTCOME MEASURES: Incidence of noninfectious uveitis. For the primary outcome, incident noninfectious uveitis was defined as a new diagnosis code for noninfectious uveitis followed by a second instance of a noninfectious uveitis code within 120 days. For the alternative outcome definition, a corticosteroid prescription or code for an ocular corticosteroid injection within 120 days of the uveitis diagnosis code was used instead of the second uveitis diagnosis code. RESULTS: There were 217 653 women exposed to FHT and 928 408 women not unexposed to FHT. For the primary outcome, the hazard ratio (HR) for incident noninfectious uveitis was not significantly different between the FHT and unexposed cohorts (HR, 0.99; 95% confidence interval [CI], 0.83-1.17; P = 0.87). With the alternative outcome definition, the FHT cohort was more likely to develop uveitis (HR, 1.21; 95% CI, 1.04-1.41; P = 0.01). When examined by anatomic subtype, for anterior uveitis there was a greater likelihood of incident uveitis in the exposed cohort (HR, 1.23; 95% CI, 1.05-1.45; P = 0.01) for the alternative outcome definition but not for the primary outcome. With age stratification, women exposed to FHT aged ≥45 years at the time of FHT prescription were more likely to develop uveitis (HR, 1.23; 95% CI, 1.03-1.47; P = 0.03) for the alternative outcome definition. A similar HR (1.22) was seen for women aged ≤44 years at the time of prescription, but this association did not meet statistical significance (P = 0.20). CONCLUSIONS: Exposure to FHT increases the rate of incident noninfectious uveitis when uveitis is defined on the basis of both diagnostic codes and documentation of corticosteroid treatment. However, the risk is modest and FHT is likely safe with regard to noninfectious uveitis risk in the majority of patients exposed to these drugs.
PURPOSE: To estimate the incidence of medication-free remission of chronic anterior uveitis and identify predictors thereof. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients diagnosed with anterior uveitis of longer than 3 months' duration followed up at United States tertiary uveitis care facilities. METHODS: Estimation of remission incidence and identification of associated predictors used survival analysis. MAIN OUTCOME MEASURES: Incidence of medication-free remission. For the primary analysis, remission was defined as inactive uveitis while off treatment at all visits spanning an interval of at least 90 days or-for patients who did not return for follow-up after 90 days-remaining inactive without receiving suppressive medications at all of the last visits. Association of factors potentially predictive of medication-free remission was also studied. RESULTS: Two thousand seven hundred ninety-five eyes of 1634 patients with chronic anterior uveitis were followed up over 7936 eye-years (4676 person-years). The cumulative medication-free, person-year remission incidence within 5 years was 32.7% (95% confidence interval [CI], 30.4%-35.2%). Baseline clinical factors predictive of reduced remission incidence included longer duration of uveitis at presentation (for 2 to 5 years vs. less than 6 months: adjusted hazard ratio [aHR], 0.61; 95% CI, 0.44-0.83), bilateral uveitis (aHR, 0.75; 95% CI, 0.59-0.96), prior cataract surgery (aHR, 0.70; 95% CI 0.56-0.88), and glaucoma surgery (aHR, 0.63; 95% CI, 0.45-0.90). Two time-updated characteristics were also predictive of reduced remission incidence: keratic precipitates (aHR, 0.36; 95% CI, 0.21-0.60) and synechiae (aHR, 0.62; 95% CI, 0.41-0.93). Systemic diagnosis with juvenile idiopathic arthritis and spondyloarthropathy were also associated with reduced remission incidence. Older age at presentation was associated with higher incidence of remission (for age ≥40 years vs. <40 years: aHR, 1.29; 95% CI, 1.02-1.63). CONCLUSIONS: Approximately one third of patients with chronic anterior uveitis remit within 5 years. Longer duration of uveitis, younger age, bilateral uveitis, prior cataract surgery, glaucoma surgery, presence of keratic precipitates and synechiae, and systemic diagnoses of juvenile idiopathic arthritis and spondyloarthropathy predict reduced remission incidence; patients with these factors should be managed taking into account the higher probability of a longer disease course.
Corneal dystrophies are broadly defined as inherited disorders that affect any layer of the cornea and are usually progressive, bilateral conditions that do not have systemic effects. The 2015 International Classification of Corneal Dystrophies classifies corneal dystrophies into four classes: epithelial and subepithelial dystrophies, epithelial-stromal TGFBI dystrophies, stromal dystrophies and endothelial dystrophies. Whereas some corneal dystrophies may result in few or mild symptoms and morbidity throughout a patient's lifetime, others may progress and eventually result in substantial visual and ocular disturbances that require medical or surgical intervention. Corneal transplantation, either with full-thickness or partial-thickness donor tissue, may be indicated for patients with advanced corneal dystrophies. Although corneal transplantation techniques have improved considerably over the past two decades, these surgeries are still associated with postoperative risks of disease recurrence, graft failure and other complications that may result in blindness. In addition, a global shortage of cadaveric corneal graft tissue critically limits accessibility to corneal transplantation in some parts of the world. Ongoing advances in gene therapy, regenerative therapy and cell augmentation therapy may eventually result in the development of alternative, novel treatments for corneal dystrophies, which may substantially improve the quality of life of patients with these disorders.
PURPOSE: To determine the preoperative characteristics, intraoperative and postoperative complications, and outcomes of eyes with posteriorly inserted vitreous base. METHODS: In this retrospective, observational, consecutive case series at 2 academic centers, 37 patients were studied who had posteriorly inserted vitreous base noted during vitrectomy. Posteriorly inserted vitreous base was defined as the insertion of the posterior hyaloid membrane being located posterior to the vortex veins. Fifteen eyes were analyzed in a histopathologic study of donor eyes to determine the average distance of the ora serrata from the vortex veins as this distance is uncertain. RESULTS: Posteriorly inserted vitreous base was identified during vitrectomy in 31 eyes with rhegmatogenous retinal detachment (84%), 4 with macular hole (11%), 1 with vitreous hemorrhage, and 1 with epiretinal membrane. Adjunctive buckle was used in 24%; 54% had 360° laser. Average number of tears seen preoperatively in those with rhegmatogenous retinal detachment was 3.1. Thirty percent had new breaks identified intraoperatively. Forty-one percent had lattice degeneration; new breaks were found in 40% of eyes with lattice. Thirteen percent of rhegmatogenous retinal detachments developed proliferative vitreoretinopathy. Average distance from the ora serrata to the vortex veins was 7.6 mm. CONCLUSION: Any eye undergoing vitrectomy may have posteriorly inserted vitreous base, but those with a high number of retinal breaks and lattice near the equator may be at highest risk. Redetachment and proliferative vitreoretinopathy still occur despite knowledge of the disorder and adjuvant treatments.
We present a case of bilateral ankyloblepharon filiforme adnatum in 1-day-old girl and describe our surgical approach. The bands connecting the upper and lower eyelids of both eyes were severed using blunt scissors. Point bleeding at the cut bands stopped in 1-2 minutes, without the need for cauterization or compression. The patient was able to open her eyes shortly after the procedure, as she woke up from anesthesia. Examination under general anesthesia showed normal eye examination appropriate for age. Postoperatively, the patient maintained open palpebral fissures. Visual development over 3 years' follow-up was normal.