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.

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.

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.

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.

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.

Dry Eye Disease Association with Computer Exposure Time Among Subjects with Computer Vision Syndrome.

PURPOSE: To assess the time of exposure to the computer and dry eye disease (DED) in subjects with computer vision syndrome (CVS). METHODS: A cross-sectional study was conducted in office workers, computer users of both sexes, with an age range of 18-45 years without comorbidities; we included 108 subjects divided into 3 groups according to the time of computer exposure in hours per day (H/D): <4 (n = 23), 4 -7.9 (n = 49), >8 (n = 39). A specific questionnaire was applied to them on the exposure time and the type of visual display terminal (VDT) used, as well as the computer vision symptoms scale (CVSS17). DED was diagnosed with the Ocular Surface Disease Index (OSDI). Ocular surface damage and signs of DED were evaluated with the tear rupture time test (TBUT), the integrity of the ocular surface by ocular surface staining (OSS) and the production of the aqueous basal tear film using the Schirmer test. RESULTS: Average computer exposure time, measured differently, was positively correlated with DED development. The computer exposure time measured in hours per year and TBUT showed a significant negative correlation (p <0.001) (rho -0.463). Years of computer exposure and staining of the ocular surface showed a significant positive correlation (p <0 0.001; rho 0.404). The accumulated exposure time was negatively correlated with TBUT (p <0.001; rho -0.376) and positively with OSS (p <0.001; rho 0.433). Schirmer test did not correlate with computer exposure time. CONCLUSION: The prolonged time of exposure to the computer in subjects with CVS was significantly correlated with the DED tests, in the different ways of measuring it; but not with the Schirmer test.

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.

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.

Resolution of giant ocular surface squamous neoplasia with topical 5-fuorouracil 1.

An 82-year-old man presented with a left eye elevated single ocular surface squamous neoplasia. The tumor involved 360° of limbus, three quadrants of cornea and conjunctiva; this was compatible with the diagnosis of giant ocular surface squamous neoplasia. Topical 5-fluorouracil 1% was planned four times daily for 1 week followed by 3 weeks off-treatment. Patient inadvertently continued 5-fluorouracil, four times daily for 4 weeks, presenting with clinical resolution of the ocular surface squamous neoplasia and subtotal corneal epithelial defect associated with 5-fluorouracil toxicity. One month later, we observed a transparent cornea and no signs of toxicity. Total tumor resolution was observed for at least 6 months of follow-up.

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.

Short-term outcomes after the loading phase of intravitreal bevacizumab and subthreshold macular laser in non-center involved diabetic macular edema.

AIM: To compare the effectiveness of intravitreal bevacizumab and subthreshold macular photocoagulation (SMP), for the treatment of non-center involved diabetic macular edema (non-CI DME). METHODS: Prospective, randomized, controlled clinical study included patients with type 2 diabetes, non-CI DME and best-corrected visual acuity (BCVA) of 0.30 logMAR or better. Each eye was randomized into three groups: group 1, monthly intravitreal bevacizumab; group 2, single SMP; group 3, single SMP and monthly bevacizumab. Main outcome measures were BCVA, and macular thickness measured with optical coherence tomography as macular central subfield thickness (CST), macular area of greater thickness (MAGT) and total macular volume (TMV). Results were analyzed after 3mo. RESULTS: A total of 32 eyes were included. Group 3 improved in BCVA (0.19±0.16 to 0.12±0.14 logMAR; P=0.041) and in TMV (7.90±0.57 to 7.65±0.73 mm3; P=0.025). Group 1 improved in MAGT (325±26.26 to 298.20±44.85 µm; P=0.022) and TMV (7.79±0.57 to 7.50±0.56 mm3, P=0.047). Group 2 didn't show significant improvement of any variable. CONCLUSION: The loading phase of bevacizumab as monotherapy or combined with SMP is superior to SMP as monotherapy in providing short-term visual and anatomical improvement in non-CI DME.

Application of Novel Drugs for Corneal Cell Regeneration.

Corneal transplantation has been the only treatment method for corneal blindness, which is the major cause of reversible blindness. However, despite the advancement of surgical techniques for corneal transplantation, demand for the surgery can never be met due to a global shortage of donor cornea. The development of bioengineering and pharmaceutical technology provided us with novel drugs and biomaterials that can be used for innovative treatment methods for corneal diseases. In this review, the authors will discuss the efficacy and safety of pharmacologic therapies, such as Rho-kinase (ROCK) inhibitors, blood-derived products, growth factors, and regenerating agent on corneal cell regeneration. The promising results of these agents suggest that these can be viable options for corneal reconstruction and visual rehabilitation.

Sex and age morphometric variations in bony nasolacrimal duct and fossa for lacrimal gland in Mexican population / Variaciones morfométricas de sexo y edad en el conducto nasolagrimal óseo y la fosa de la glándula lagrimal en la población mexicana

Primary acquired nasolacrimal duct obstruction is greater in women over 40 years and has been associated with morphometric variations in the osseous nasolacrimal duct, which varies according to age and sex. The objective is to determine variations regarding sex and age of the nasolacrimal duct and osseous fossa for lacrimal gland. One hundred sixteen dry orbits from Mexican population were analyzed; subdivided into four groups based on age and sex. The length, transverse and anteroposterior diameters of the bone entrance of the nasolacrimal duct, and the length and width of the fossa for lacrimal gland were determined. Statistical tests were applied to determine the significance of the differences found between groups. The nasolacrimal duct in women had shorter length than men in both age groups. The entrance had a wider transverse diameter in women than men independently of age and its anteroposterior diameter was shorter in men under 40 years than over 40 years. The fossa for lacrimal gland was larger in women under 40 years than in men of same age group and women over 40 years old. The lower third of the was wider in women under 40 years than in women over 40 years. Our study confirms significant differences between sex and age groups in some of the morphometric measurements of bony nasolacrimal duct and fossa for lacrimal gland in Mexican population. Comparative studies with and without clinical illness are needed to clarify if the bony characteristics of those structures participate in the etiopathogenesis and distribution differences observed in sex, age and ethnicity of thisillness.

La obstrucción de la vía lagrimal inferior es mayor en mujeres mayores de 50 años y se ha asociado a variaciones morfométricas en la entrada ósea del conducto nasolagrimal (CNL), las cuales varían según edad y sexo. El objetivo del presente estudio es determinar las variaciones respecto a sexo y edad de los diámetros de la entrada ósea del CNL, longitud del CNL y fosa de la glángula lagrimal (FL) ósea. Se analizaron 116 órbitas secas de población mexicana, los cuales a su vez fueron subdivididos en dos subgrupos en base a la edad y sexo. Se determinaron los diámetros transverso y anteroposterior de la entrada ósea del CNL, la longitud del CNL y la longitud y anchura de la FL. Se aplicaron pruebas estadísticas para determinar la significancia de las diferencias entre los grupos de estudio. La longitud del CNL fue menor en mujeres que en hombres en ambos grupos de edad. En cuanto a la entrada ósea del CNL, el diámetro transverso de fue significativamente menor en hombres que en mujeres independientemente de la edad y el diámetro anteroposterior fue menor en hombres < 40 que en > 40. La longitud de la FL fue mayor en mujeres < 40 años que en hombres del mismo rango de edad y que en mujeres > 40 años. La anchura de la FL en el tercio inferior fue menor en mujeres > 40 años que < 40 años. El resto de las mediciones de la FL no presentó diferencias significativas por sexo ni grupo de edad. Nuestro estudio confirmó que existen diferencias entre sexo y grupo de edad en algunas mediciones morfométricas del CNL y FL óseas en población mexicana. Se necesitan estudios comparativos entre personas con y sin obstrucción clínica de vía lagrimal inferior para esclarecer si las características óseas de estas estructuras participan o no en la etiopatogenia y las diferencias de distribución en género, edad y etnia de esta enfermedad.