Eye and lid involvement as an uncommon feature of pemphigus foliaceus in a pediatric patient.

Pemphigus foliaceus (PF) is an autoimmune blistering disorder which affects the superficial layers of the epidermis with rare mucosal involvement. We present the case of a 12-year-old girl with PF involving the eyes and eyelids. A literature review of pediatric nonendemic PF revealed another two cases with ocular manifestations. Eyelid involvement is an uncommon feature of PF that should be properly identified and treated.

Lessons Learned From Ocular Graft versus Host Disease: An Ocular Surface Inflammatory Disease of Known Time of Onset.

ABSTRACT: The ocular surface inflammatory disorders (OSIDs) comprise a group of conditions characterized by persistent inflammation of the ocular surface and adnexal tissues. Systemic autoimmune diseases and hypersensitivity reactions cause them, and, if left untreated, can result in severe inflammatory dry eye, corneal damage, and vision loss. Ocular graft-versus-host disease (oGVHD) forms part of the ocular surface inflammatory disease umbrella. It is a condition occurring after allogeneic hematopoietic stem cell or bone marrow transplantation, usually in chronic graft-versus-host disease. oGVHD can virtually affect any ocular adnexal tissue, especially the meibomian glands, and cause persistent inflammation, tissue fibrosis, and subsequent chronic, severe dry eye disease. Among the OSIDs, oGVHD has the particularity that it has a "time zero," meaning we know when the disease started. As such, preclinical models have leveraged this to investigate the molecular mechanisms involved in the damage oGVHD causes to the ocular surface. In oGVHD, establishing a "time zero" allows for predicting the clinical course and establishing adequate treatment. This is also possible because the inflammatory infiltration occurs in ocular surface tissues, which are readily accessible. Using oGVHD, we might be able to understand the immune response mechanisms in other OSIDs better (i.e., Sjögren syndrome, Stevens-Johnson syndrome, among others). This review presents an up-to-date overview of the pathogenesis, clinical presentation, and treatment of oGVHD. In addition, we will discuss the value of the "time zero" concept in the study of oGVHD.

Expression of growth hormone and growth hormone receptor genes in human eye tissues.

In humans, the polygenic growth hormone (GH) locus is located on chromosome 17 and contributes with three types of proteins: pituitary GH which consists of at least two isoforms one of 22 kDa and the other of 20 kDa, placental GH, which also exhibits isoforms, and chorionic somatomammotropin hormone (CSH). While pituitary GH results from the expression of the GH-1 (GH-N) gene, placental GH is produced by the expression of the GH-2 (GH-V) gene and CSH is contributed by expression of the CSH-1 and CSH-2 genes. The location where GH-1 is expressed is the anterior pituitary and the rest of the genes in the locus are expressed in placenta. On the other hand, expression and synthesis of GH in extra-pituitary tissues, including the eye, has been recently described. However, the physiological role of GH in the eye has not yet been elucidated, although a possible neuroprotective role has been hypothesized. Thus, we analyzed GH-1, GH-2, CSH1/2, Pit-1, GHR, GHRH, GHRHR, SST, SSTR1, SSTR2, SSTR3, SSTR4, and SSTR5 to elucidate the expression and regulation of the GH locus in the human eye. Through qPCR analysis, we only found evidence of GH-1 expression in retina, choroid and trabecular meshwork; its transcript turned out to be the same as pituitary GH mRNA found in major species, and no splicing variants were detected. PIT1 was absent in all the ocular tissues implying an independent GH-1 expression mechanism. We found evidence of GHR in the cornea, choroid coat and retina. These results suggest autocrine and/or paracrine regulation, possibly exerted by GHRH and SSTs (since their mRNAs and receptors were found predominantly in retinal, choroidal and corneal tissues) since expression of both molecules was detected in different ocular tissues, as well as in the same tissues where GH-1 expression was confirmed. Our results add solid evidence about the existence of a regulatory local system for GH expression and release in the human eye.

Olfactomedin-like 2 A and B (OLFML2A and OLFML2B) profile expression in the retina of spotted gar (Lepisosteus oculatus) and bioinformatics mining.

Olfactomedin-like (OLFML) proteins are members of the olfactomedin domain-containing secreted glycoprotein (OLF) family. OLFML2A and OLFML2B are representative molecules of these glycoproteins. Olfactomedins are critical for the development and functional organization of the nervous system and retina, which is a highly conserved structure in vertebrates, having almost identical anatomical and physiological characteristics in multiple taxa. Spotted gar, a member of the Lepisosteidae family, is a freshwater fish that inhabits rivers, bayous, swamps, and brackish waters. Recently, the complete genome has been sequenced, providing a unique bridge between fish medical models to human biology, making it an excellent animal model. This study was aimed to understanding the evolution OLFML2A and OLFML2B in the retina of spotted gar through looking for the expression of these genes. Spotted gar retina was analyzed with hematoxylin-eosin staining assays to provide an overall view of the retina structure and an immunofluorescence assay to identify OLFML2A and OLFML2B protein expression. A phylogenetic tree was created using the neighbor-joining method. Forces that direct the evolution of the fish genes were tested. Spotted gar retina, as in other vertebrates, is made of several layers. OLFML2A and OLFML2B proteins were detected in the rod and cone photoreceptor layer (PRL), outer nuclear layer (ONL), and inner nuclear layer (INL). Phylogenetic tree analysis confirms the orthology within the OLFML2A gene. Purifying selection is the evolutionary force that directs the OLFML2A genes. OLFML2A genes have a well-conserved function over time and species.

Expression of growth hormone gene in the baboon eye.

The human growth hormone (GH) locus is comprised by two GH (GH1 and GH2) genes and three chorionic somatomammotropin (CSH1, CSH2 and CSH-L) genes. While GH1 is expressed in the pituitary gland, the rest are expressed in the placenta. However, GH1 is also expressed in several extrapituitary tissues, including the eye. So to understand the role of this hormone in the eye we used the baboon (Papio hamadryas), that like humans has a multigenic GH locus; we set up to investigate the expression and regulation of GH locus in adult and fetal baboon ocular tissues. We searched in baboon ocular tissues the expression of GH1, GH2, CSH1/2, Pit1 (pituitary transcription factor 1), GHR (growth hormone receptor), GHRH (growth hormone releasing hormone), GHRHR (growth hormone releasing hormone receptor), SST (somatostatin), SSTR1 (somatostatin receptor 1), SSTR2 (somatostatin receptor 2), SSTR3 (somatostatin receptor 3), SSTR4 (somatostatin receptor 4), and SSTR5 (somatostatin receptor 5) mRNA transcripts and derived proteins, by qPCR and immunofluorescence assays, respectively. The transcripts found were characterized by cDNA cloning and sequencing, having found only the one belonging to GH1 gene, mainly in the retina/choroid tissues. Through immunofluorescence assays the presence of GH1 and GHR proteins was confirmed in several retinal cell layers. Among the possible neuroendocrine regulators that may control local GH1 expression are GHRH and SST, since their mRNAs and proteins were found mainly in the retina/choroid tissues, as well as their corresponding receptors (GHRH and SSTR1-SSTR5). None of the ocular tissues express Pit1, so gene expression of GH1 in baboon eye could be independent of Pit1. We conclude that to understand the regulation of GH in the human eye, the baboon offers a very good experimental model.

Olfactomedin-like 2 A and B (OLFML2A and OLFML2B) expression profile in primates (human and baboon).

BACKGROUND: The olfactomedin-like domain (OLFML) is present in at least four families of proteins, including OLFML2A and OLFML2B, which are expressed in adult rat retina cells. However, no expression of their orthologous has ever been reported in human and baboon. OBJECTIVE: The aim of this study was to investigate the expression of OLFML2A and OLFML2B in ocular tissues of baboons (Papio hamadryas) and humans, as a key to elucidate OLFML function in eye physiology. METHODS: OLFML2A and OLFML2B cDNA detection in ocular tissues of these species was performed by RT-PCR. The amplicons were cloned and sequenced, phylogenetically analyzed and their proteins products were confirmed by immunofluorescence assays. RESULTS: OLFML2A and OLFML2B transcripts were found in human cornea, lens and retina and in baboon cornea, lens, iris and retina. The baboon OLFML2A and OLFML2B ORF sequences have 96% similarity with their human's orthologous. OLFML2A and OLFML2B evolution fits the hypothesis of purifying selection. Phylogenetic analysis shows clear orthology in OLFML2A genes, while OLFML2B orthology is not clear. CONCLUSIONS: Expression of OLFML2A and OLFML2B in human and baboon ocular tissues, including their high similarity, make the baboon a powerful model to deduce the physiological and/or metabolic function of these proteins in the eye.

Clinical and surgical implications regarding morphometric variations of the medial wall of the orbit in relation to age and gender.

The ethmoidal foramens are located on the medial wall of the orbit and are key reference points for intraoperative orientation. Detailed knowledge of the anatomy, bony landmarks and morphometric characteristics of the medial wall of the orbit is essential for various surgical procedures. The aim of this study was to determine the morphometric variations in the medial wall of the orbit and establish significant variations regarding age and gender. A total of 110 orbits were analyzed and subdivided by age (over or under 40 years) and gender. The distances of the medial wall of the orbit between the anterior lacrimal crest, the ethmoidal foramen, the optic canal and the interforamina were determined. Safe surgical areas were sought. Statistical tests were used to determine the differences between groups. In men, there is a safe surgical area proximal to the anterior and posterior ethmoidal foramen. In women, this area is in the posterior third of the medial wall of the orbit between the posterior ethmoidal foramen and the optic canal. Regarding variation according to age, the results of this study suggested that the anteroposterior diameter of the medial wall increases with age. This study showed that the anteroposterior total length of the medial orbit wall is similar between genders of similar age, increases with age, and has significant variations in the distances between the various structures that make up the medial orbit wall with regard to gender and age.

Conjunctival infection with Chlamydia trachomatis in sexual partners of patients with adult inclusion conjunctivitis.

To compare the incidence of conjunctival infection with Chlamydia trachomatis in sexual partners of patients with newly diagnosed adult inclusion conjunctivitis (AIC) and a control group with healthy eyes. We also compare the observed signs and symptoms of conjunctival infection in patients with newly diagnosed AIC and their sexual partners. We performed a prospective comparative case-control study between patients with newly diagnosed AIC confirmed with direct fluorescent antibody (DFA) (n = 11), their sexual partners (n = 11), and a control group of healthy subjects (n = 11). Clinical history, physical examination, and a DFA test for C. trachomatis of a conjunctival scrapping from the tarsal conjunctiva were performed in all patients. A significantly higher frequency of positive DFA tests for C. trachomatis was observed in the sexual partner group (n = 8, 73 %) compared with the healthy control group (n = 2, 18.2 %) (P = 0.03). Ocular symptoms and signs were observed significantly more often in patients from the confirmed clinically active AIC group (n = 11, 100 %) than in their sexual partners (n = 2, 12.5 %). Sexual partners of patients with AIC are at greater risk of having an asymptomatic conjunctival infection with C. trachomatis than healthy subjects. Sexual partners might be considered a bacterial reservoir and a possible source for chlamydia reinfection. Not treating sexual partners might increase the probability of reinfection. More extended studies with a greater sample size should be done.

Femtosecond laser applications in corneal surgery.

Femtosecond laser (FSL) applications in corneal surgery have increased since its inception. Corneal surgery has undergone a tremendous transformation thanks to the introduction of FSL technology. This laser makes precise, three-dimensional incisions while causing minimal damage to surrounding tissue. This review updates and summarizes current and upcoming FSL applications in corneal surgery, current commercially available FSL, and its respective applications. Refractive surgery applications include laser in-situ keratomileusis flaps, refractive corneal lenticule extraction such as small incision lenticule extraction, astigmatic keratotomy, intracorneal ring segments tunnels for keratoconus including corneal allogenic intrastromal ring segments, and presbyopia treatments with intrastromal pockets for corneal inlays and intrastromal incisions (INTRACOR). Keratoplasty applications include penetrating keratoplasty trephination; superficial and deep anterior lamellar keratoplasty trephination, lamellar dissection, and tunnel creation; posterior lamellar keratoplasty donor and recipient preparation; Bowman layer transplantation donor, and recipient preparation; and stromal keratophakia. Other applications include conjunctival graft preparation in pterygium surgery, and keratopigmentation (corneal tattooing). FSL is a surgical instrument widely used in corneal surgery because it improves reproducibility and safety in many procedures.

Face Mask and Tear Film Stability: A Pilot Study of the Objective Measurement of Tear Break-Up Time.

(1) Background: Mask-associated dry eye (MADE) has been associated with increased dry eye symptoms, apparently due to reduced tear break-up time (TBUT). This study aimed to determine the short-term impact of surgical face mask (FM) on tear film stability by measuring non-invasive tear break-up time (NIBUT). (2) Methods: Twenty-six healthy participants had NIBUT evaluated without FM, with surgical FM and with a surgical FM secured to the skin with adhesive tape (TFM). NIBUT-first was measured with Keratograph 5M (K5M, Oculus, Wetzlar, Germany). Each participant had NIBUT measured in four sessions on four consecutive days. Session 1: without FM vs. with FM. Session 2: with FM vs. without FM. Session 3: without FM vs. with TFM. Session 4: with TFM vs. without FM (3). The time between each measured setting was 2 min. Results: The mean ± SD NIBUT without FM was 8.9 ± 3.7, with FM 10.2 ± 4.1, and with TFM 8.4 ± 3.8 s. No significant differences were observed in NIBUT in any of the evaluated settings: without FM vs. with FM (p = 0.247), without FM vs. with TFM (p = 0.915), and with FM vs. with TFM (p = 0.11). (4) Conclusions: This study did not find a significant short-term effect of FM on NIBUT. Other variables or longer periods of exposure might trigger the symptoms and ocular surface alterations in MADE.

TFOS Lifestyle: Impact of the digital environment on the ocular surface.

Eye strain when performing tasks reliant on a digital environment can cause discomfort, affecting productivity and quality of life. Digital eye strain (the preferred terminology) was defined as "the development or exacerbation of recurrent ocular symptoms and/or signs related specifically to digital device screen viewing". Digital eye strain prevalence of up to 97% has been reported, due to no previously agreed definition/diagnostic criteria and limitations of current questionnaires which fail to differentiate such symptoms from those arising from non-digital tasks. Objective signs such as blink rate or critical flicker frequency changes are not 'diagnostic' of digital eye strain nor validated as sensitive. The mechanisms attributed to ocular surface disease exacerbation are mainly reduced blink rate and completeness, partial/uncorrected refractive error and/or underlying binocular vision anomalies, together with the cognitive demand of the task and differences in position, size, brightness and glare compared to an equivalent non-digital task. In general, interventions are not well established; patients experiencing digital eye strain should be provided with a full refractive correction for the appropriate working distances. Improving blinking, optimizing the work environment and encouraging regular breaks may help. Based on current, best evidence, blue-light blocking interventions do not appear to be an effective management strategy. More and larger clinical trials are needed to assess artificial tear effectiveness for relieving digital eye strain, particularly comparing different constituents; a systematic review within the report identified use of secretagogues and warm compress/humidity goggles/ambient humidifiers as promising strategies, along with nutritional supplementation (such as omega-3 fatty acid supplementation and berry extracts).

Application of Intraoperative Optical Coherence Tomography Technology in Anterior Segment Surgery.

The use of optical coherence tomography (OCT) technology in anterior segment diseases allows for precise assessment of the changes following anterior segment surgery. Advances in microscope-integrated OCT systems have allowed the utilization of intraoperative OCT (iOCT) in anterior segment surgeries, i.e., cornea, cataract, and refractive surgery. iOCT has enabled real-time precise visualization of anterior segment tissues as well as interactions between surgical instruments and ocular tissue; thus, the device can facilitate surgical procedures and provide valuable information for decision-making during anterior segment surgeries. In this review, the authors will introduce studies regarding the development of iOCT technology and its application in various anterior segment surgeries. Multiple studies have shown the efficacy of the iOCT for intraoperative assistance and guidance, suggesting the potential of the device for optimizing the surgical outcomes after cornea, cataract, and refractive surgery.

Reduced corneal endothelial cell density after toxic anterior segment syndrome (TASS) caused by inadvertent intraocular ointment migration: A case report.

INTRODUCTION AND IMPORTANCE: Toxic anterior segment syndrome (TASS) is an acute sterile inflammation of the anterior segment which may occur after surgery. This case presents endothelial cell density (ECD) loss due to months of TASS caused by intraocular migration of ocular ointment. The chronicity of this case and the clinical consequences are rare in the literature. CASE PRESENTATION: A Colombian 71-year-old man developed TASS secondary to intraocular ointment migration after uneventful cataract surgery with phacoemulsification and intraocular lens placement in the capsular bag. The main complaint for the patient was a chronic red eye, no pain or visual disturbance were reported, rheumatologic diseases were discarded. It was documented the presence of intraocular ointment in the anterior chamber, over the iris and in the anterior chamber angle. The ECD was reduced secondary to TASS and the long-term presence of ointment moving in the anterior chamber, so it had to be removed. CLINICAL DISCUSSION: It is important to avoid using ocular ointment after intraocular surgeries to avoid the risk of ointment migration into the anterior chamber. Intraocular ointments should be removed promptly to reduce ECD loss as documented in the present case report in which after ointment elimination ECD remains stable for 7 years. CONCLUSION: Topical ointments should not be used after routine cataract surgery because of the risk of intraocular ointment migration and subsequent risk of developing TASS and reduced ECD.

Patient-reported experience of dry eye management: An international multicentre survey.

PURPOSE: To explore the journey taken by patients in a range of different countries to manage their dry eye symptoms. METHOD: Members of the general public who responded positively to the question "Do your eyes ever feel dry?" completed a questionnaire describing their demographics, the impact of their symptomology, the advice they have received and the management options they have tried. The Ocular Surface Disease Index (OSDI) questionnaire was also completed. RESULTS: A total of 916 individuals (Canada = 235, Mexico = 127, New Zealand = 157, Taiwan = 246, UK = 151) of similar age distribution (median 38 years, IQR: 27-50) completed the survey. The reported duration of symptoms was longest in Canada (median 4 years, range 2-10) and least in Taiwan (2 years, range 1-3; p < 0.001), and similar trends were observed for symptom severity (p = 0.001). However, there was no statistically significant difference between countries with respect to the impact of symptoms on quality of life (median 3/10; p = 0.08). Less than half of the individuals in any country had consulted with a health professional. About half had tried a treatment for their dry eye symptoms, with artificial tears being the most common treatment, followed by warm compresses, and both therapies were rated as reasonably effective (median 5-7/10). CONCLUSION: Many people with dry eye symptoms are not consulting health care professionals who can confirm the diagnosis, exclude differential diagnoses, and offer a wide range of treatments targeted at the dry eye subtype.

Cornea lenticule viability and structural integrity after refractive lenticule extraction (ReLEx) and cryopreservation.

PURPOSE: To assess and compare keratocyte viability and collagen structure in cornea stroma lenticules collected immediately after refractive lenticule extraction (ReLEx) and one month after cryopreservation. METHODS: The fresh and cryopreserved human stroma lenticules procured after ReLEx were processed for ultrastructural analysis of keratocytes and collagen fibrils with transmission electron microscopy (TEM), apoptotic cell detection with deoxynucleotidyl transferase-mediated nick end labeling assay (TUNEL) assay, and cultured for keratocyte-specific gene expression analysis using reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: The periphery of the lenticule had greater TUNEL-positive cells compared to the center of the lenticule in both fresh and cryopreserved groups. There was an increase in TUNEL-positive cells after cryopreservation, which was significantly higher in the center of the lenticule, but not in the periphery. TEM showed apoptotic, necrotic and viable quiescent keratocytes in fresh and cryopreserved lenticules. Collagen analysis with TEM showed a well preserved and well aligned structure in fresh and cryopreserved lenticules; without significant change in the total number of collagen fibrils but with an increased collagen fibril density (CFD) after cryopreservation. In vitro, isolated keratocytes derived from fresh and cryopreserved lenticules exhibited a typical fibroblastic phenotype. RT-PCR showed a positive gene expression for keratocan (KERA) and aldehyde dehydrogenase 3A1 (ALDH3A1) in cells isolated from fresh and cryopreserved lenticules. CONCLUSIONS: The stromal lenticules extracted from ReLEx surgery remain viable after cryopreservation. Although they showed a decrease in CFD, the collagen architecture was preserved and there was good cellular viability.

Advances in Imaging Technology of Anterior Segment of the Eye.

Advances in imaging technology and computer science have allowed the development of newer assessment of the anterior segment, including Corvis ST, Brillouin microscopy, ultrahigh-resolution optical coherence tomography, and artificial intelligence. They enable accurate and precise assessment of structural and biomechanical alterations associated with anterior segment disorders. This review will focus on these 4 new techniques, and a brief overview of these modalities will be introduced. The authors will also discuss the recent advances in research regarding these techniques and potential application of these techniques in clinical practice. Many studies on these modalities have reported promising results, indicating the potential for more detailed comprehensive understanding of the anterior segment tissues.

Relationship of Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratio With Visual Acuity After Surgical Repair of Open Globe Injury.

Purpose: To assess the relationship and prognostic value of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) with poor final best-corrected visual acuity (BCVA) after surgical repair of open globe injuries (OGI) in adults. Design: Retrospective analysis of data from an ongoing prospective cohort of consecutive patients. Methods: In a tertiary university hospital, 197 eyes of 197 patients were included between 2013 and 2017. NLR and PLR were obtained from pre-operative blood tests to analyze its relationship with poor final BCVA. Results: Severe visual impairment (SVI) was defined as ≤20/200, and was observed in 96 (48.7%) patients after surgical repair of OGI. SVI patients had higher NLR (7.4 ± 6.6 vs. 4.0 ± 3.2, p < 0.001), and PLR (167 ± 92 vs. 139 ± 64; p = 0.021) than non-SVI. NLR ≥ 3.47 and PLR ≥ 112.2 were the best cut-off values for SVI, were univariate risk factors for SVI, and had sensitivity: 69.0, 71.4, and specificity: 63.6, 44.8, respectively. In multivariate analysis, only OTS, athalamia, and hyphema remained as risk factors. NLR had significant correlation with ocular trauma score (OTS) (r = -0.389, p < 0.001) and final BCVA (r = 0.345, p < 0.001). Limitations: Simultaneous trauma in other parts of the body that could influence the laboratory findings. Conclusion: Patients with SVI after a repaired OGI had increased pre-operative NLR and PLR levels. High NLR and PLR are risk factors for SVI in univariate analysis. It is confirmed that low OTS is a risk factor for SVI. High NLR and PLR could be used as a prognostic tool to identify patients at higher risk for SVI after repair of OGI.

Objective Imaging Diagnostics for Dry Eye Disease.

Traditional diagnostic tests for dry eye disease (DED), such as fluorescein tear film break-up time and the Schirmer test, are often associated with poor reproducibility and reliability, which make the diagnosis, follow-up, and management of the disease challenging. Advances in ocular imaging technology enables objective and reproducible measurement of changes in the ocular surface, tear film, and optical quality associated with DED. In this review, the authors will discuss the application of various imaging techniques, such as, noninvasive tear break-up time, anterior segment optical coherence tomography, in vivo confocal microscopy, meibography, interferometry, aberrometry, thermometry, and tear film imager in DED. Many studies have shown these devices to correlate with clinical symptoms and signs of DED, suggesting the potential of these imaging modalities as alternative tests for diagnosis and monitoring of the condition.

Application of Femtosecond Laser in Anterior Segment Surgery.

Femtosecond laser (FSL) is a near-infrared laser that can create reliable and reproducible tissue cutting with minimal damage to adjacent tissue. As the laser can also create incisions with various orientations, depths, and shapes, it is expected to be a useful tool for anterior segment surgery, such as cornea, refractive, and cataract surgery. In this review, the authors will introduce the application of FSL in various anterior segment surgeries and discuss the results of studies regarding the efficacy and safety of FSL in cornea, refractive, and cataract surgery. Experimental studies regarding the potential use of FSL will also be introduced. The studies discussed in this review suggest that FSL may be a useful tool for improving the prognosis and safety of surgeries of the anterior segment.