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Purpose To report a case series of subjective and objective hearing function changes associated with teprotumumab treatment for thyroid eye disease. Observations A 74-year-old female with a history of Graves' disease with thyroid eye disease was treated with teprotumumab. She had a history of bilateral tinnitus and noticed a subjective improvement in her tinnitus after the second infusion. Audiology testing obtained before, during, and after completion of infusions showed symmetric and rapidly progressive worsening of the patient's sensorineural hearing loss. In contrast, a 42-year-old male with a history of Grave's disease endorsed worsening intermittent tinnitus and low-pitched hearing loss after initiation of teprotumumab. Audiology testing before, during, and after completion of infusions showed stable and normal hearing function bilaterally. Conclusion and importance This case series highlights the importance of objective testing in patients prior to and after teprotumumab initiation as subjective hearing changes may not accurately reflect objective hearing function. In addition, this report suggests that teprotumumab may play a role in potentiating sensorineural hearing loss.

Purpose: To describe steps taken that enabled a high rate of retention and early resumption of enrollment in the Zoster Eye Disease Study (ZEDS), a randomized controlled trial funded by the National Eye Institute, during the first 13 months (3/1/2020-3/31/2021) of the COVID-19 pandemic. Methods: A number of responses were implemented in ZEDS when the focus shifted to retention of study participants at the beginning of the pandemic including frequent communication with the participating clinical centers (PCCs) about remote visits, local lab work, shipping study medication, and completion of revised case report forms. Additional payments were provided to the PCCs. Remote activation of PCCs continued. Screening and enrollment visits gradually resumed when allowed. Results: Communication with PCCs increased, and average attendance at monthly coordinator teleconferences went up from 17 to 47. Remote visits peaked in April 2020, accounting for 75% (33/44) of study visits, then declined to less than 10% of study visits beginning August 2020. Overall, 97% (590/609) of study visits were completed. Only 5.5% (9/165) of study participants withdrew consent, and 2.4% (4/165) were lost to follow-up. Enrollment returned to pre-pandemic levels by September 2020. Discussion: Strong communication and unwavering commitment, combined with the technological capability for remote work, visits, and shipment of study medication, were key to the successful retention of study participants and resumption of enrollment. Conclusions: Rapid responses to challenges to trials caused by the COVID-19 pandemic can enable them to continue successfully and provide insights into the planning of future trials.

Effectively inhibiting subconjunctival fibrosis remains a challenge in pterygium and antiglaucoma surgery. As one of the superior first-line clinical drugs, 5-fluorouracil (5-FU) possesses certain disadvantages, such as fast drug metabolism and poor dose controllability. The emergence of appropriate pharmaceutical formulation and administration routes provides attractive solutions. In this work, we report the development of a multilevel drug release strategy using two types of nature-derived biomaterials (biocompatible chitosan and silk protein) processed into nanofibers of different size ranges, which was shown to achieve sustained release of 5-FU, toward the unique application of inhibiting subconjunctival fibrosis. In vitro data demonstrated that this system achieved fast 5-FU release during the first 25 days, where the release became relatively stable and lengthy (3 months) afterward. More importantly, the in vivo outcomes also suggested a continuous long-lasting inhibitory effect on subconjunctival myofibroblasts. These results indicated that our nature-derived bionanomaterials served as a promising drug-carrying platform for inhibiting subconjunctival fibrosis by providing sustained release of pharmaceutical compounds thus reducing the administration frequency, which may find broad utility in the treatment of ocular diseases and possibly other biomedical applications.

Purpose Descemet's membrane endothelial keratoplasty (DMEK) is becoming the gold standard to treat corneal endothelial dysfunctions worldwide. Compared with conventional penetrating keratoplasty, infectious complications after DMEK are ill defined. We describe the clinical picture of 2 DMEK recipients, operated on the same day and in the same clinic, who developed atypical herpes simplex virus type 1 (HSV-1) infection in the transplant recipient eye within days post-DMEK. Because recipients received cornea tissue from 2 different donors prepared by the same eye bank, the likelihood of a common HSV-1 source was determined. Design Case series. Participants Two DMEK recipients who developed atypical intraocular HSV-1 disease shortly after surgery and surplus cornea specimens of 6 donors. Methods Surplus cornea donor (pre-DMEK cornea remnants and conditioned cornea storage and transport media) and recipient samples (post-DMEK aqueous humor) were assayed for HSV-1 DNA and infectious virus by real-time polymerase chain reaction (RT-PCR) and cell culture, respectively. Target-enriched whole viral genome sequencing was performed on HSV-1 DNA–positive ocular specimens. Main Outcome Measures Clinical picture of atypical intraocular HSV-1 infection post-DMEK and presence and homology of HSV-1 genomes between ocular specimens of DMEK donors and recipients. Results Herpes simplex virus type 1 DNA was detected in aqueous humor and donor cornea specimens of both DMEK cases, but not in the cornea remnants of 6 randomly selected donors processed by the same eye bank. Infectious HSV-1 was isolated from the cornea remnant and corresponding culture medium of 1 cornea donor. Notably, whole-genome sequencing of virus DNA-positive specimens demonstrated exceptionally high genetic similarity between HSV-1 strains in recipient and donor specimens of both DMEK cases. Conclusions Data indicate cross-contamination of cornea grafts during DMEK preparation with subsequent graft-to-host HSV-1 transmission that caused atypical sight-threatening herpetic eye disease shortly after DMEK. Ophthalmologists should be aware that HSV-1 transmission by DMEK is possible and can lead to atypical ocular disease, a condition that can easily be prevented by taking appropriate technical and clinical measures at both eye bank and surgical levels.

Ocular albinism type 1 is a genetic eye disease caused by mutations in the GPR143 gene. Little is known about the molecular pathways involved in this disease and no therapeutic candidate has been identified as yet. Here we report the generation of an iPSC line from the skin fibroblasts of a patient with a mutation in the GPR143 gene using Sendai Virus vectors. This new iPSC line will allow a better understanding of the Ocular Albinism type 1 disease and to screen for potential therapeutic candidates.

Purpose To study post-interventional findings in patients with dysthyroid optic neuropathy (DON) treated with teprotumumab. Observations In this multicenter observational Case series, patients with DON were treated with teprotumumab, an insulin-like growth factor I receptor inhibitor (10 mg/kg for the first infusion then 20 mg/kg for subsequent infusions, every three weeks for a total 8 infusions). This study included patients with acute and chronic thyroid eye disease (TED) with DON who had failed conventional therapies and were not candidates for surgical decompression. Data collected included best corrected visual acuity (BCVA), color vision, RAPD when present, and orbital CT or MRI. Proptosis, clinical activity score (CAS), Gorman diplopia score (GDS), and Humphrey visual fields (HVF) were also evaluated. Ten patients (6 women, 4 men) with an average age 64 years old were included in this study. Mean follow up after completion of infusions was 15 weeks. Baseline visual acuity (VA) impairment ranged from hand motion (HM) to 20/25 in affected eyes. All patients had pre-treatment orbital CT or MRI that confirmed orbital apex compression. Seventy percent of patients had objective improvement in DON after 2 infusions of teprotumumab measured as significant improvement in visual acuity, resolution of RAPD, or both. After completion of treatment, affected eyes had a mean BCVA improvement of 0.87 logMAR (p=0.0207), proptosis reduction of 4.7 mm (p, Highlights • Teprotumumab is effective for the treatment of dysthyroid optic neuropathy. • Most patients demonstrated rapid objective improvement after 2 infusions. • Visual acuity improved and relative afferent pupillary defect resolved after treatment. • Orbital imaging showed improvement of orbital apex crowding after treatment. • Patients with longstanding severe vision loss had limited improvement in visual acuity.

Background Age-related macular degeneration (AMD) is one of the leading causes of vision loss in the elderly population. The application of artificial intelligence (AI) provides convenience for the diagnosis of AMD. This systematic review and meta-analysis aimed to quantify the performance of AI in detecting AMD in fundus photographs. Methods We searched PubMed, Embase, Web of Science and the Cochrane Library before December 31st, 2020 for studies reporting the application of AI in detecting AMD in color fundus photographs. Then, we pooled the data for analysis. PROSPERO registration number: CRD42020197532. Findings 19 studies were finally selected for systematic review and 13 of them were included in the quantitative synthesis. All studies adopted human graders as reference standard. The pooled area under the receiver operating characteristic curve (AUROC) was 0.983 (95% confidence interval (CI):0.979–0.987). The pooled sensitivity, specificity, and diagnostic odds ratio (DOR) were 0.88 (95% CI:0.88–0.88), 0.90 (95% CI:0.90–0.91), and 275.27 (95% CI:158.43–478.27), respectively. Threshold analysis was performed and a potential threshold effect was detected among the studies (Spearman correlation coefficient: -0.600, P = 0.030), which was the main cause for the heterogeneity. For studies applying convolutional neural networks in the Age-Related Eye Disease Study database, the pooled AUROC, sensitivity, specificity, and DOR were 0.983 (95% CI:0.978–0.988), 0.88 (95% CI:0.88–0.88), 0.91 (95% CI:0.91–0.91), and 273.14 (95% CI:130.79–570.43), respectively. Interpretation Our data indicated that AI was able to detect AMD in color fundus photographs. The application of AI-based automatic tools is beneficial for the diagnosis of AMD. Funding Capital Health Research and Development of Special (2020–1–2052).

Purpose To present a case of ulcerative colitis associated with teprotumumab treatment for thyroid eye disease. Observations A 46-year-old Indian female was treated with teprotumumab (Tepezza) for severe thyroid eye disease within 9 months of diagnosis. The patient noted progression of her disease on oral prednisone and demonstrated severe, debilitating proptosis accompanied by eye ache and dry eyes. After 5 infusions of teprotumumab over a four-month period, the patient developed bloody diarrhea and fecal urgency. These symptoms progressively worsened and after two additional treatments, she underwent a colonoscopy. This confirmed the diagnosis of ulcerative colitis (UC). Treatment with teprotumumab was halted prior to the administration of the 8th infusion; however, the patient continued to have severe gastrointestinal symptoms two months after her last treatment. Conclusions and importance Teprotumumab is an insulin-like growth factor-1 receptor (IGF-1R) inhibitor demonstrated to improve proptosis in patients with active thyroid eye disease. Most adverse events reported are mild or moderate in severity; however, inflammatory bowel disease (IBD) is a serious adverse event that can develop as a result of treatment.

Purpose To report two cases of thyroid eye disease (TED) associated compressive optic neuropathy (CON) that resolved after treatment with teprotumumab. Observation Two patients presented with active TED resulting in mild CON with the typical corresponding visual field (VF) defects. Both patients were initiated on intravenous (IV) corticosteroid therapy but despite treatment had persistent VF defects. Both patients were then treated with teprotumumab and demonstrated marked clinical improvement and complete resolution of TED-CON VF defects early in their infusion course. Conclusions and importance These cases suggest that teprotumumab can be a rapid and effective treatment for TED-CON, and raises the question of whether it may be superior to IV corticosteroid therapy.

Diseases of the retina are common and numerous, with causes ranging over inherited, inflammatory, vascular, infectious, neoplastic, traumatic, toxic, and idiopathic etiologies. A key issue in the diagnosis of retinal disease is the duration of symptoms, which can be acute, chronic, or acute presentations of chronic disease. Clinical examination with direct ophthalmoscopy or, even better, biomicroscopy with a slit lamp and condensing lens, is a key component of diagnosis, which can be enhanced through investigational methods such as fluorescein angiography, optical coherence tomography, or electroretinography. Consideration of the history, visual acuity and visual field, and fundoscopic findings is usually sufficient to determine whether patients need referral on an emergency, urgent, or routine basis. Emphasis is given to vascular disease, age-related macular degeneration, diabetic retinopathy, genetic eye disease, and retinal detachment.

This chapter describes indications, contraindications, patient selection factors, and outcomes for orbital decompression surgery. Patients who may benefit from surgery are typically first identified by the ophthalmologist. Orbital decompression surgery is most commonly indicated for the treatment of thyroid eye disease refractory to nonsurgical interventions, specifically steroid treatment and radiation therapy. Urgent indications include dysthyroid optic neuropathy, which presents with vision loss, and severe corneal exposure. Nonurgent indications include diplopia, proptosis, orbital and retrobulbar pain, and ocular hypertension. There are no absolute contraindications to orbital decompression surgery, although the standard factors in determining surgical candidacy, such as comorbid conditions, apply. The specific indications and contraindications for surgery crucially influence the decision-making process regarding the optimal timing of the surgery, the surgical plan, such as the specific bony walls to address, and the key clinical outcomes, which can include visual acuity, proptosis, and/or diplopia. Recent research has also been focused on determining relevant radiographic-based outcomes, and there has been an increasing emphasis on quality-of-life outcomes, for orbital decompression surgery.

Purpose: Periorbital myxedema is one the most challenging symptoms for patients with Graves' eye disease (GED). The treatment of this condition is complex and often unsatisfactory. This case demonstrates the use of intralesional hyaluronidase to treat cosmetically concerning periorbital myxedema. Observations: Follow up showed no clinically significant recurrence of myxedema over one year. Conclusion: Intralesional hyaluronidase represented an effective and safe treatment of periorbital myxedema in a patient with Graves' eye disease.

Purpose To report the first case of a patient with chronic thyroid eye disease (TED) treated with teprotumumab. Observations A 50-year-old female with a 3-year history of Graves’ disease presented with bilateral exophthalmos greatest on the left side. She was followed for 2 years with stable proptosis measurements (23mm OD, 28mm OS). Her clinical activity score (CAS) was 1 and there were no examination findings reflective of active inflammation. The patient underwent systemic treatment with teprotumumab and despite chronic TED and low CAS, she had notable improvement in proptosis (18mm OD, 22mm OS) and decrease in extraocular muscle volume as noted on orbital imaging. Conclusion and importance This case report suggests that teprotumumab may be used in patients with chronic TED and low CAS. Improvement in the proptosis and reduction in extraocular muscle volume suggest that teprotumumab may alter disease course even in patients with inactive or quiescent TED.

The detrimental effects of perfluoroalkyl substances (PFASs) on several physiological systems have been reported, but the association of PFASs with eye, one of the most sensitive and exposed organ, has never been explored. To investigate the association between eye diseases including visual impairment (VI) and PFASs isomers, a cross-sectional stratified study was conducted in 1202 Chinese population, aged 22–96 years, from Shenyang, China. A standard protocol including Snellen vision chart, slit-lamp microscopy and direct ophthalmoscopy was used to examine eye diseases/conditions relating to anterior and posterior segment of eyes. In addition, we measured the blood concentrations of 19 linear and branched PFASs at one-time point. Results indicated that blood levels of PFASs were significantly higher in eye disease group than normal group. PFASs exposure were positively associated with both combined eye diseases and individual eye diseases. Among other PFASs, linear perfluorooctane sulfonate (n-PFOS; odds ratio [OR] = 3.37, 95% confidence interval [CI]: 2.50, 4.56), branched perfluorooctane sulfonate (Br-PFOS; OR = 2.25, 95% CI: 1.72, 2.93) and linear perfluorooctanoic acid (n-PFOA; OR = 1.79, 95% CI: 1.36, 2.37) significantly increases the odds of VI. Vitreous disorder was adversely associated with long-chain PFASs exposure. For example, perfluorotridecanoic acid (PFTrDA; OR = 1.86, 95% CI: 1.51, 2.29) and perfluorodecanoic acid (PFDA; OR = 1.79, 95% CI: 1.36, 2.36) showed the most significant association. In conclusion, this study suggests higher serum PFASs levels were associated with increase odds of VI and vitreous disorder in Chinese adults. Keywords: Perfluoroalkyl substances (PFASs), PFASs isomers, Eye diseases, Visual impairment, Vitreous disorder

Retinal images are a key factor for ophthalmologists in the diagnosis of several eye diseases, with a sign of a microvascular retina, which occurs in response to high blood pressure and diabetes. Periodic ophthalmoscopy is the best approach for eye disease screening. However, the number of ophthalmologists available is a limiting factor in initiating screening. With the availability of digital fundus cameras, for automatic analysis of digital images, it can help ophthalmologists diagnose eye disease. On the other hand, computer science, especially in-depth learning has the ability to identify objects in many domains, one of which is the identification of objects in images including images of the retina of the eye. This chapter explains the application of depth learning approach to classification of eye diseases based on color fundal images as inputs. Subsequently, in the Fundus Imaging subchapter, we will discuss the acquisition of relevant Images, major vascular and nonvascular abnormalities, assessment of hypertensive retinopathy and diabetes. In the last section, we implemented convolutional neural networks (CNN) as classifiers for retinal images. The public database used in this study is retinal color images from the STARE dataset which are resized to 61 × 70, 46 × 53, and 31 × 35 pixels. This dataset is categorized into 15 classes of eye diseases. Our experiments show that the highest training accuracy is obtained from input images measuring 61 × 71 and 31 × 35 pixels. The highest test accuracy obtained from the network configuration used is the size of the input image with the smallest resolution of 31 × 35 pixels with an accuracy of 80.93%.

In many developing countries, diabetes prevalence is growing rapidly due to the changing lifestyle of people. The loss of blood circulation or blood supply in blood vessels is called macular ischemia which may cause permanent vision loss. Image processing is a technique by which we can diagnose eye disease. Macular ischemia is a slow process of blockage of small blood vessels including veins in retina due to insufficient blood supply to macula. Our proposed methodology offers information of retinal blood vessel morphology compared with diameter of normal expected blood vessel and locates small and tiny blood vessel abnormalities or irregularities that describe the blood vessel pathology. The system uses Graph Trace Algorithm technique for extracting features and vessel segmentation. The system also uses KNN algorithm for the classification of arteries and veins to find blockage in veins. Then apply support vector machine (SVM) to classify severity grading of retinal images in shorter time and for better accuracy.

A significant number of individuals suffer from hereditary ocular disorders and age-related vision impairments and that number is expected to double as the population ages. With the recent advancements in gene therapy shown to be effective in treating some forms of eye disease, it has become clinically relevant to provide accurate genetic diagnosis in these cases. However, considerable genetic overlap between clinical phenotypes necessitates tailored genetic testing approaches to identify the underlying causes. Furthermore, multiple classes of pathogenic variants have been associated with ocular disorders, which include coding and non-coding changes, copy number variation (CNV), and chromosomal aberrations each requiring specific sequencing strategies, while follow-up experimentation is required to fully assess their pathogenicity. This chapter discusses current methods to detect and analyze genetic variants leading to eye disease with the ultimate goal of identifying therapeutic targets for treatment.

Age-related macular degeneration (AMD) causes a severe loss of sight. AMD is an eye disease related to retina. Macular degeneration is the leading cause of vision loss, more than any other eye diseases. AMD is a chronic disease and it cannot be cured. There are two types of macular degeneration namely; wet macular degeneration (WMD) and dry macular degeneration (DMD). The fundus imaging technique, optical coherence tomography (OCT) technique are the imaging modalities, used to detect AMD. OCT is a known technology for detection of AMD because it will detect minute changes in the retina. By extracting RPE layer, one can find out the healthy or affected AMD using image processing tools. In the dry age-related macular degeneration (DAMD), there will be existence of small yellow deposits and in wet age-related macular degeneration (WAMD), there will be an irregular growth of blood vessels under the layer of macula. These conditions result in intensity variations in fundus images which could form the basis for screening and diagnosis of the disease.

Recent evidence from the literature suggests that a gut–eye–lacrimal gland axis exists, as the microbiome can influence ocular health and inflammation. Studies have shown that germ-free mice spontaneously develop dry eyes and that an animal model of Sjogren syndrome displays increased lacrimal gland inflammation, when raised in a germ-free environment. Furthermore, patients with Sjogren syndrome have decreased intestinal bacterial diversity, which correlates with the systemic severity score of disease. Recent studies probing the connection between the microbiome and the eye and the possibility of using fecal transplants in modulating eye disease will be discussed.

The congenital disorders of glycosylation (CDG) are a family of anabolic diseases with variable multisystem manifestations. Most of these disorders have multisystem manifestations, in addition to a wide variety of neurologic phenotypes. The most frequent type is PMM2-CDG (phosphomannomutase deficiency), which is associated with severe cerebellar atrophy, intellectual disability, stroke-like episodes and seizures, and progressive pigmentary retinopathy and demyelinating neuropathy in classic cases. Other phenotypes have considerable overlap, and with few exceptions, are accompanied by varying systemic manifestations that may include coagulopathies, gastrointestinal disease, lipodystrophy, skeletal deformities, cardiac, renal, and eye disease. CDG should be suspected in any patient with multisystem disease and neurologic manifestations, and can be efficiently screened for in most cases using carbohydrate deficient transferrin. Enzyme analysis is clinically available for the more common disorders, and molecular diagnosis is rapidly improving for all forms of CDG. Specific therapy is available for MPI-CDG and SLC365C1-CDG.

Purpose: To determine the distribution of iris color and its relationship with some ocular diseases in a rural population of Iran. Methods: Two rural areas of the north and southwest of Iran were selected by a cross-sectional study using multi-stage cluster sampling. After selecting samples, the participants had an eye examination including measuring visual acuity, refraction, and Pentacam imaging. Then an eye examination for individuals was performed by slit-lamp. Results: Out of 3851 invited people, 3314 participated in this study (participation rate, 86.05%). Dark brown [41.28%, confidence interval (CI) 95% = 31.88–50.68] and blue (0.99%, CI 95% = 0.57–1.41) were the most and the least type of iris colors among participants of this study. Compared to others, people with a dark iris have the biggest anterior chamber depth (ACD), angle and volume while central corneal thickness (CCT), keratometry and pupil were highest among people with a dark brown iris (P

Purpose: To report the successful use of tofacitinib in the treatment of refractory uveitis and scleritis. Observations: Two patients, one with scleritis and another with anterior and intermediate uveitis, presented with refractory disease after failure of multiple steroid-sparing therapies. Treatment with tofacitinib led to durable resolution of uveitis and scleritis. Conclusions and importance: Tofacitinib is a potential novel treatment option for refractory, noninfectious inflammatory eye disease. Keywords: Uveitis, Scleritis, Tofacitinib, JAK, STAT

The prevalence of many eye diseases, including cataracts, age-related macular degeneration and diabetic retinopathy, is expected to increase and has become leading causes of irreversible vision loss in the elderly population. Recent experimental and clinical studies have increased awareness of the potential health benefits of polyphenol consumption, including for the prevention of chronic eye diseases. This review focuses on recent findings regarding the beneficial effects of polyphenols for treatment/prevention of cataracts, age-related macular degeneration, diabetic retinopathy and glaucoma, and discusses possible mechanisms of action. The results of studies presented in this review show that polyphenols suppress formation of reactive oxygen species, increase antioxidant defense systems, ameliorate pro-inflammatory cytokines, and decrease vascular endothelial growth factor in retinal cells and ocular tissues. Based on these results, polyphenols may be an effective and safe component of functional foods used to address chronic eye disease.

Introduction: Congenital central hypoventilation syndrome (CCHS) is a very rare genetic disease. In 2012 the European Central Hypoventilation Syndrome (EuCHS) Consortium created an online patient registry in order to improve care. Aim: To determine the characteristics and outcomes of Spanish patients with CCHS, and detect clinical areas for improvement. Materials and method: An assessment was made on the data from Spanish patients in the European Registry, updated on December 2015. Results: The Registry contained 38 patients, born between 1987 and 2013, in 18 hospitals. Thirteen (34.2%) were older than 18 years. Three patients had died. Genetic analysis identified PHOX2B mutations in 32 (86.5%) out of 37 patients assessed. The 20/25, 20/26 and 20/27 polyalanine repeat mutations (PARMs) represented 84.3% of all mutations. Longer PARMs had more, as well as more severe, autonomic dysfunctions. Eye diseases were present in 47%, with 16% having Hirschsprung disease, 13% with hypoglycaemia, and 5% with tumours. Thirty patients (79%) required ventilation from the neonatal period onwards, and 8 (21%) later on in life (late onset/presentation). Eight children (21%) were using mask ventilation at the first home discharge. Five of them were infants with neonatal onset, two of them, both having a severe mutation, were switched to tracheostomy after cardiorespiratory arrest at home. Approximately one-third (34.3%) of patients were de-cannulated and switched to mask ventilation at a mean age of 13.7 years. Educational reinforcement was required in 29.4% of children attending school. Conclusion: The implementation of the EuCHS Registry in Spain has identified some relevant issues for optimising healthcare, such as the importance of genetic study for diagnosis and assessment of severity, the high frequency of eye disease and educational reinforcement, as well as some limitations in ventilatory techniques. Resumen: Introducción: El síndrome de hipoventilación central congénita (SHCC) es una enfermedad genética muy rara causada por mutaciones en PHOX2B; en 2010 se creó el Consorcio Europeo del Síndrome de Hipoventilación Central, que en 2012 implantó un Registro online de pacientes para optimizar su cuidado. Objetivo: Conocer las características y la evolución de los pacientes españoles con SHCC y detectar áreas de mejora. Materiales y método: Se analizaron los datos actualizados en diciembre del 2015 de los pacientes españoles del Registro europeo. Resultados: Se registró a 38 pacientes, nacidos entre 1987 y 2013, procedentes de 18 hospitales. El 34,2% eran mayores de 18 años. Han fallecido 3 pacientes. Aportaban estudio del gen PHOX2B 37 (97,3%), 32 (86,5%) con mutación. Los genotipos 20/25, 20/26 y 20/27 representaron el 84,3% de las mutaciones. Las disautonomías fueron más frecuentes y graves en portadores de genotipos con mayores expansiones de polialaninas. El 47% de pacientes asociaba alteraciones oculares, el 16% Hirschsprung, el 13% hipoglucemias y el 5% tumores. Treinta pacientes (79%) debutaron en el periodo neonatal y 8 (21%) posteriormente (inicio/diagnóstico tardío). Ocho niños (21%) recibieron inicialmente ventilación domiciliaria con mascarilla; 5 eran lactantes con comienzo neonatal, 2 de ellos precisaron cambio a traqueostomía tras presentar parada cardiorrespiratoria; ambos tenían mutaciones graves. Han sido decanulados y transferidos a mascarilla el 34,3% de los pacientes (edad media: 13,7 años). El 29,4% de los niños escolarizados precisaron refuerzo educativo. Conclusión: La implementación del Registro en España de pacientes con SHCC ha permitido identificar aspectos relevantes para optimizar sus cuidados, tales como la importancia del estudio genético para el diagnóstico y la estimación de gravedad, la frecuencia elevada de alteraciones oculares y de necesidad de refuerzo educativo, y algunas limitaciones de las técnicas ventilatorias.

Melatonin is not only synthesized by the pineal gland but by several ocular structures. This natural indoleamine is of great importance for regulating several eye processes, among which pressure homeostasis is included. Glaucoma, the most prevalent eye disease, also known as the silent thief of vision, is a multifactorial pathology that is associated to age and, often, to intraocular hypertension (IOP). Indeed IOP is the only modifiable risk factor and as such medications are available to control it; however, novel medications are sought to minimize undesirable side effects. Melatonin and analogues decrease IOP in both normotensive and hypertensive eyes. Melatonin activates its cognate membrane receptors, MT1 and MT2, which are present in numerous ocular tissues, including the aqueous-humor-producing ciliary processes. Melatonin receptors belong to the superfamily of G-protein-coupled receptors and their activation would lead to different signalling pathways depending on the tissue. This review describes the molecular mechanisms underlying differential functionalities that are attributed to melatonin receptors. Accordingly, the current work highlights the important role of melatonin and its analogues in the healthy and in the glaucomatous eyes, with special attention to the control of intraocular pressure.

Purpose: The clinical features of autoimmune retinopathy (AIR) can resemble and be difficult to differentiate from inherited retinal degenerations (IRDs). Misdiagnosis of an IRD as AIR causes unnecessary treatment with immunosuppressive agents. The purpose of this study is to calculate the predictive value of genetic testing for IRDs in patients with suspected AIR and provide clinical examples where genetic testing has been useful. Methods: We identified patients seen at MEEI between April 2013 and January 2017 for whom the differentiation of AIR vs. IRDs was difficult based on clinical assessment alone. All patients had some atypical features for AIR, but tested positive for anti-retinal antibodies. Within this group, we identified six patients who had genetic testing for IRDs with the Genetic Eye Disease panel for retinal genes (GEDi-R). We calculated the positive predictive value (PPV) and negative predictive value (NPV) of genetic testing in a population with approximately equal numbers of IRD and AIR patients. Results: Six patients had clinical features that made distinguishing between IRDs and AIR on a clinical basis difficult and were sent for genetic testing: four women and two men with a mean age of 59.5 years. In two of these six patients, genetic diagnoses were made based upon the identification of known pathogenic variants in the common IRD genes USH2A and RHO. Two patients had variants of unknown significance within genes associated with IRDs, and the other two had no relevant genetic findings. Given the 60% sensitivity and 3% false positive rate for GEDi-R testing and assuming a 50% pre-test probability of having an IRD, the PPV for GEDi-R for detecting IRD is 95.2% and the NPV is 70.8%. Conclusions and Importance: In patients for whom the differential diagnosis of AIR and IRDs is unclear based on clinical information, genetic testing can be a valuable tool when it identifies an IRD, sparing the patient unnecessary immunosuppressive treatment. However, the test has a low NPV so a negative genetic testing result does not confidently exclude IRD as the true diagnosis. Keywords: Autoimmune retinopathy, Cancer associated-retinopathy, Genetic testing, Inherited retinal degeneration

Fuchs endothelial corneal dystrophy (FECD) is a bilateral inherited eye disease with advanced forms only treatable by corneal transplantation. The pathogenesis of FECD has not been worked out yet, however, trinucleotide repeat polymorphism CTG18.1 in the TCF4 gene has recently been associated with late-onset FECD. Gene expression profiling of corneal endothelium with and without this expansion can help elucidate molecular mechanisms of the disease development. Current data article represents whole transcriptome profiles of corneal endothelium obtained from 12 patients with FECD and 6 control tissues from eye bank donors. RNA sequencing data is available at NCBI Sequence Read Archive under Accession No. PRJNA524323. In addition, each patient and donor were genotyped for CTG18.1 expansion and the corresponding numbers of CTG repeats in the TCF4 gene are provided within this article. The dataset includes samples from FECD patients both with and without CTG18.1 expansion. Keywords: Fuchs endothelial corneal dystrophy, RNA-Seq, Transcriptome

Summary Background Hepatitis D is the most severe form of chronic viral hepatitis. Treatment guidelines recommend 1 year of peginterferon alfa, which is effective in 25–30% of patients only. Whether prolonged therapy with peginterferon alfa-2a for 96 weeks and combination therapy with tenofovir disoproxil fumarate (TDF) would increase hepatitis D virus (HDV) RNA suppression is unknown. We aimed to explore whether prolonged treatment of HDV with 96 weeks of peginterferon would increase HDV RNA response rates and reduces post-treatment relapses. Methods We did two parallel, investigator-initiated, multicentre, double-blind randomised, controlled trials at 14 study sites in Germany, Greece, Romania, and Turkey. Patients with chronic HDV infection and compensated liver disease who were aged 18 years or older were eligible for inclusion. All patients were HBsAg positive for at least 7 months, anti-HDV positive for at least 3 months, and HDV-RNA positive at the local laboratory at the screening visit. Patients were ineligible if alanine aminotransferase levels were higher than ten times above the upper limit of normal and if platelet counts were lower than 90 000 per μL, or if they had received interferon therapy or treatment with a nucleoside and nucleotide analogue within the preceding 6 months. Patients were randomly assigned by blinded stratified block randomisation (1:1) to receive 180 μg of peginterferon alfa-2a weekly plus either TDF (300 mg once daily) or placebo for 96 weeks. The primary endpoint was the percentage of patients with undetectable HDV RNA at the end of treatment assessed by intention to treat. The trials are registered as NCT00932971 and NCT01088659 . Findings Between June 24, 2009, and Feb 28, 2011, we randomly assigned 59 HDV RNA-positive patients to receive peginterferon alfa-2a plus TDF and 61 to receive peginterferon alfa-2a plus placebo, including 48 (40%) patients with cirrhosis to the two treatment groups (23 in the peginterferon alfa-2a plus TDF group and 25 in the peginterferon alfa-2a plus placebo group). The primary endpoint was achieved in 28 (48%) of 59 patients in the peginterferon alfa-2a plus TDF group and in 20 (33%) of 61 patients in the peginterferon alfa-2a plus placebo group (odds ratio 1·84, 95% CI 0·86–3·91, p=0·12). We recorded 944 adverse events (459 in the peginterferon alfa-2a plus TDF group and 485 in the peginterferon alfa-2a plus placebo group). The most common adverse events were haematological, behavioural (eg, fatigue), musculoskeletal, influenza-like syndromes, and psychiatric complaints. Interpretation Addition of TDF resulted in no significant improvement in HDV RNA response rates at the end of treatment. These findings highlight that alternative treatment options are needed for hepatitis D. Funding The HepNet Study-House (a project of the German Liver Foundation founded by the German Liver Foundation, the German Ministry for Education and Research, and the German Center for Infectious Disease Research), Hoffmann-La Roche, and Gilead Sciences.

That diet can influence eye health has been recognized for centuries, but the role of specific nutrients has only recently begun to be understood. Vitamin A, the first essential dietary component identified in the early 20th century, was isolated and proven to be the critical lipid factor in liver and dairy products that prevented night blindness and keratomalacia, two eye conditions that often accompany more generalized malnutrition. Since the 1980s, results from epidemiological studies and clinical trials have suggested nutrients and non-nutritive diet components that slow the development of human age-related eye diseases—cataract, macular degeneration, and diabetic retinopathy—and animal and cell culture studies have elucidated the mechanisms for many of these effects. Unique to the eye is the concentrated exposure to sunlight that can cause direct photochemical damage and exacerbate oxidative stress and inflammation, which also promote chronic eye disease. Evidence indicates that a variety of dietary substances may protect against cataract, age-related macular degeneration, and diabetic retinopathy through the lowering of oxidative stress, inflammation, hyperglycemia, hypertension, and inappropriate angiogenesis. Nutrients thought to protect against chronic eye disease are discussed and include carotenoids lutein and zeaxanthin, zinc, vitamin C, vitamin E, omega-3 fatty acids, and vitamin D. A variety of non-nutritive food substances may influence eye health but are less well understood. However, single nutrient strategies for lowering the onset and progression of eye diseases are not likely to be as effective as strategies that involve nutrient-rich diet patterns as part of a healthy lifestyle. Evidence from clinical trials and observational studies suggests that introducing nutrient-rich dietary patterns and physical activity slow the destructive physiological processes that contribute to aging of the eye and are more likely than single nutrients to improve eye health as people age. Research is also emerging about the potential importance of obtaining lutein and zeaxanthin early in life. Specific levels of nutrients or types of nutrient-rich dietary patterns needed for optimal eye health and vision throughout life are largely unknown and likely depend on other aspects of lifestyle and genetic makeup.

Aim To describe the first case of a secondary meningioma in a patient after radiation treatment for thyroid eye disease (TED). Secondarily to identify any additional cases of secondary malignancy resulting from radiotherapy for thyroid eye disease from our institutional experience. Background Thyroid eye disease (TED) is a self-limiting auto-immune disorder causing expansion of orbital soft tissue from deposition of glycosaminoglycans and collagen, leading to significant cosmetic and functional morbidity. Established management options for TED include: glucocorticosteroids, orbital radiotherapy, and surgical orbital decompression. Two large series on radiotherapy for TED have been reported without any cases of secondary malignancy. Materials and methods The case of a patient with visual failure, found to have a sphenoid wing meningioma after previous TED radiotherapy is described. We then reviewed 575 patients with at least 3-year follow-up receiving radiotherapy for TED at British Columbia Cancer Agency to identify other possible secondary malignancies. Results The patient had postoperative improvement in her vision without any identified complications. Three additional cases of hematologic malignancy were identified. The calculated risk in our population of developing a radiation-induced meningioma after TED with at least 3 years of follow-up of is 0.17% (1/575); with hematopoetic malignancies the risk for secondary malignancy is 0.7% (4/575). Conclusions Our calculated risk for secondary malignancy (0.17%, 0.7%) is similar to the reported theoretical risk published in the literature (0.3–1.2%). There is real risk for the development of a secondary malignancy after radiotherapy treatment of TED and treatment options should include consideration for this potential.

Background: To determine the relationship between central corneal thickness (CCT), refractive error, corneal curvature, anterior chamber depth and axial length in normal Taiwanese Chinese adults. Methods: Five hundred normal Taiwanese Chinese patients aged 40–80 years were recruited for the study. Measurement procedures included CCT, refractive error, corneal curvature, anterior chamber depth and axial length. Exclusion criteria were previous ocular surgery, glaucoma, trauma history, external eye disease, and previous contact lens use. The relationships among parameters were tested using Pearson’s correlation and linear regression analysis. Results: The median CCT was 555 ± 27 μm for males and 553 ± 30 μm for females. Eyes with more myopic refractive error tended to have greater axial length (r =− 0.645, p < 0.001). Eyes with axial elongation tended to have flatter cornea (r =− 0.502, p < 0.001) and deeper anterior chamber (r = 0.651, p < 0.001). There were no significant correlations between the CCT and refractive error (r =− 0.034, p = 0.445), corneal curvature (r = 0.013, p = 0.770), anterior chamber depth (r = 0.023, p = 0.614) and axial length (r =− 0.053, p = 0.223). Conclusion: CCT was not associated with refractive error, corneal curvature, anterior chamber depth and axial length. CCT is an independent factor unrelated to other ocular parameters. [J Chin Med Assoc 2009;72(3):133–137]

Purpose To estimate the incidence of and investigate possible risk factors for postkeratoplasty atopic sclerokeratitis in keratoconus patients undergoing keratoplasty. Design Retrospective, noncomparative, interventional case series. Participants Two hundred forty-seven eyes with keratoconus. Methods We reviewed the medical records of all keratoplasty cases of keratoconus between May 2000 and December 2005 at Tokyo Dental College Ichikawa General Hospital. The incidence and clinical details of cases consistent with postkeratoplasty atopic sclerokeratitis were recorded. Main Outcome Measures Cases with acute sclerokeratitis during the early postoperative period were retrospectively evaluated. Results A total of 247 keratoconus eyes were followed at our clinic after keratoplasty (mean follow-up, 18.5±13.0 months). Thirty-five eyes of 29 patients (14.2%) had a history of atopic dermatitis, of which 6 eyes of 5 patients (2.4%) developed postkeratoplasty atopic sclerokeratitis. Mean age of postkeratoplasty atopic sclerokeratitis patients was 29 years (range, 23–39). The mean period between keratoplasty and onset of postkeratoplasty atopic sclerokeratitis was 26 days (range, 11–41). Loosening of running sutures and wound leakage were observed in 3 eyes; persistent epithelial defects in 3 eyes; and graft melting in 2 eyes, 1 of which was perforated. Preoperative atopic blepharitis and corneal neovascularization were identified as risk factors for postkeratoplasty atopic sclerokeratitis. Conclusions Postkeratoplasty atopic sclerokeratitis is a potentially severe complication in atopic patients undergoing keratoplasty. Systemic immunosuppression may be considered in patients with active blepharitis and corneal neovascularization.

La necrólisis epidérmica tóxica (NET) y el síndrome de Stevens-Johnson (SSJ) se describen como variantes de una misma enfermedad con diferente severidad y constituyen las reacciones cutáneas más frecuentes en niños con una considerable morbilidad. Varias comunicaciones apoyan el uso de la inmunoglobulina intravenosa (IGIV) para el tratamiento de tales entidades. Nosotros presentamos el caso de 2 pacientes, uno con NET y uno con SSJ en quienes se utilizó inmunoglobulina con resultados exitosos. Además hacemos una revisión de la evolución de 13 pacientes con NET y SSJ en los últimos 10 años en el Hospital Infantil de México en quienes se utilizó tratamiento convencional. : Toxic epidermal necrolysis and Stevens-Johnson syndrome are described as variants of the same disease with distinct severity and constitute the most frequent cutaneous reactions in children, causing considerable morbidity. Several reports support the use of intravenous immunoglobulin therapy in these entities. We report the cases of two patients, one with toxic epidermal necrolysis and the other with Stevens-Johnson syndrome, in whom immunoglobulin treatment was successfully used. We also reviewed the outcomes of 13 patients with toxic epidermal necrolysis and Stevens-Johnson syndrome in the previous 10 years in the Hospital Infantil de Mexico, in whom conventional treatment was used.