'BLUES' procedure for assessing the blue level of the sclera in Osteogenesis Imperfecta.

PURPOSE: Blue sclera is a characteristic and common clinical sign of Osteogenesis Imperfecta (OI). However, there is currently no widely accepted, objective method for assessing and grading blue sclera in individuals with OI. To address this medical need, this study is aimed to design and validate a new method called 'BLUES' (BLUe Eye Sclera) to objectively identify and quantify the blue color in the sclera of patients affected by OI. METHODS: Sixty-two patients affected by OI and 35 healthy controls were enrolled in the present prospective study, for a total of 194 eyes analyzed. In the 'BLUES' procedure, eye images from patients with OI and control subjects were analyzed to assess and grade the blue level of the sclera using Adobe Photoshop Software. The validation process then involved comparing the results obtained with the 'BLUES' procedure to the judgement of experienced ophthalmologists (JEO). A receiver-operating characteristic (ROC) curve analysis was used to examine the overall discriminatory power. The sensitivity and specificity levels and the Cohen's Kappa (K) indexes of 'BLUES' and 'JEO' were estimated versus the standard OI diagnosis. The K indexes of 'BLUES' versus 'JEO' were also evaluated. RESULTS: The optimal cut-off point of the scleral blue peak was calculated at 17%. Our findings demonstrated a sensitivity of 89% (CI95%: 0.835-0.945) and specificity of 87% (CI95%: 0.791-0.949) for the 'BLUES' procedure with an agreement versus the diagnosis of OI of 0.747. In comparison, the sensitivity and specificity of 'JEO' ranged from 89 to 94% and 77% to 100%, respectively, with an agreement ranging from 0.663 to 0.871 with the diagnosis of OI. The agreement between 'BLUES 'and 'JEO' evaluations ranged from 0.613 to 0.734. CONCLUSIONS: Our findings demonstrated an 89% sensitivity and an impressive 87% specificity of our method to analyze the blue sclera in OI. The results indicated high agreement with disease diagnosis and were consistent with evaluations by experienced ophthalmologists. The 'BLUES' procedure appears to be a simple, reliable and objective method for effectively identify and quantify the blue color of the sclera in OI.

Local resection via partial lamellar sclerouvectomy for ciliary body tumors - a case series.

BACKGROUND: Ciliary body tumor is extremely rare and treatment is challenging. The aim of this study is to present our experience in treating this rare entity, especially large tumors with more than 5 clock hours of involvement, and to evaluate the surgical outcomes and complications of local resection via partial lamellar sclerouvectomy in four cases of ciliary body tumors in China. METHODS: Four patients with ciliary body tumors underwent partial lamellar sclerouvectomy between October 2019 and April 2023 in Shanghai General Hospital, China. Tumor features, histopathologic findings, complications, visual acuity, and surgical outcomes were reviewed at a mean follow-up of 20.8 months. RESULTS: Four patients with a mean age of 31.8 years were included in this study. The histopathological diagnosis was adenoma of non-pigmented ciliary epithelium (ANPCE), schwannoma, and multiple ciliary body pigment epithelial cysts. The mean largest tumor base diameter was 6.00 mm (range: 2.00-10.00) and the mean tumor thickness was 3.50 mm (range: 2.00-5.00). Preoperative complications included cataract in 3 (75%) eyes, lens dislocation in 2 (50%), and secondary glaucoma in 1 (25%). Temporary ocular hypotonia was observed in one case and no other postoperative complications were observed. At a mean follow-up of 20.8 months, the best corrected visual acuity increased in 3 eyes and was stable in 1 eye. Tumor recurrence was absent in all eyes. All patients were alive at the end of follow-up. CONCLUSIONS: Local tumor resection via PLSU is useful in the treatment of ciliary body tumors, including large tumors occupying more than five clock hours of pars plicata. Surgery-related complications were manageable with adequate preoperative assessment and careful operation during surgery.

Polarization-Sensitive OCT Imaging of Scleral Abnormalities in Eyes With High Myopia and Dome-Shaped Macula.

Importance: The relevance of visualizing scleral fiber orientation may offer insights into the pathogenesis of pathologic myopia, including dome-shaped maculopathy (DSM). Objective: To investigate the orientation and density of scleral collagen fibers in highly myopic eyes with and without DSM by polarization-sensitive optical coherence tomography (PS-OCT). Design, Setting, and Participants: This case series included patients with highly myopic eyes (defined as a refractive error ≥6 diopters or an axial length ≥26.5 mm) with and without a DSM examined at a single site in May and June 2019. Analysis was performed from September 2019 to October 2023. Exposures: The PS-OCT was used to study the birefringence and optic axis of the scleral collagen fibers. Main Outcomes and Measures: The orientation and optic axis of scleral fibers in inner and outer layers of highly myopic eyes were assessed, and the results were compared between eyes with and without a DSM. Results: A total of 72 patients (51 [70.8%] female; mean [SD] age, 61.5 [12.8] years) were included, and 89 highly myopic eyes were examined (mean [SD] axial length, 30.4 [1.7] mm); 52 (58.4%) did not have a DSM and 37 (41.6%) had a DSM (10 bidirectional [27.0%] and 27 horizontal [73.0%]). Among the 52 eyes without DSM, the 13 eyes with simple high myopia had primarily inner sclera visible, displaying radially oriented fibers in optic axis images. In contrast, the entire thickness of the sclera was visible in 39 eyes with pathologic myopia. In these eyes, the optic axis images showed vertically oriented fibers within the outer sclera. Eyes presenting with both horizontal and bidirectional DSMs had clusters of fibers with low birefringence at the site of the DSM. In the optic axis images, horizontally or obliquely oriented scleral fibers were aggregated in the inner layer at the DSM. The vertical fibers located posterior to the inner fiber aggregation were not thickened and appeared thin compared with the surrounding areas. Conclusions and Relevance: This study using PS-OCT revealed inner scleral fiber aggregation without outer scleral thickening at the site of the DSM in highly myopic eyes. Given the common occurrence of scleral pathologies, such as DSM, and staphylomas in eyes with pathologic myopia, recognizing these fiber patterns could be important. These insights may be relevant to developing targeted therapies to address scleral abnormalities early and, thus, mitigate potential damage to the overlying neural tissue.

3D printed fibroblast-loaded hydrogel for scleral remodeling to prevent the progression of myopia.

Pathologic myopia has seriously jeopardized the visual health of adolescents in the past decades. The progression of high myopia is associated with a decrease in collagen aggregation and thinning of the sclera, which ultimately leads to longer eye axis length and image formation in front of the retina. Herein, we report a fibroblast-loaded hydrogel as a posterior scleral reinforcement (PSR) surgery implant for the prevention of myopia progression. The fibroblast-loaded gelatin methacrylate (GelMA)-poly(ethylene glycol) diacrylate (PEGDA) hydrogel was prepared through bioprinting with digital light processing (DLP). The introduction of the PEGDA component endowed the GelMA-PEGDA hydrogel with a high compression modulus for PRS surgery. The encapsulated fibroblasts could consistently maintain a high survival rate during 7 days of in vitro incubation, and could normally secrete collagen type I. Eventually, both the hydrogel and fibroblast-loaded hydrogel demonstrated an effective shortening of the myopic eye axis length in a guinea pig model of visual deprivation over three weeks after implantation, and the sclera thickness of myopic guinea pigs became significantly thicker after 4 weeks, verifying the success of sclera remodeling and showing that myopic progression was effectively controlled. In particular, the fibroblast-loaded hydrogel demonstrated the best therapeutic effect through the synergistic effect of cell therapy and PSR surgery.

The enigma of sclera-specific autoimmunity in scleritis.

Scleritis is a severe and painful ophthalmic disorder, in which a pathogenic role for collagen-directed autoimmunity was repeatedly suggested. We evaluated the presence of sclera-specific antibodies in a large cohort of patients with non-infectious scleritis. Therefore, we prospectively collected serum samples from 121 patients with non-infectious scleritis in a multicenter cohort study in the Netherlands. In addition, healthy (n = 39) and uveitis controls (n = 48) were included. Serum samples were tested for anti-native human type II collagen antibodies using a validated enzyme-linked immunosorbent assay (ELISA). Further, sclera-specific antibodies were determined using indirect immunofluorescence (IIF) on primate retinal/scleral cryosections. Lastly, human leukocyte antigen (HLA) typing was performed in 111 patients with scleritis. Anti-type II collagen antibodies were found in 13% of scleritis patients, in 10% of healthy controls and in 11% of uveitis controls (p = 0.91). A specific reaction to scleral nerve tissue on IIF was observed in 33% of patients with scleritis, which was higher than in healthy controls (11%; p = 0.01), but similar to uveitis controls (25%; p = 0.36). Reactivity to the scleral nerve tissue was significantly associated with earlier onset of scleritis (48 versus 56 years; p < 0.001), bilateral involvement (65% versus 42%; p = 0.01), and less frequent development of scleral necrosis (5% versus 22%; p = 0.02). HLA-B27 was found to be twice as prevalent in patients with scleritis (15.3%) compared to a healthy population (7.2%). In conclusion, scleral nerve autoantibody reactivity was more common in scleritis and uveitis patients in contrast to healthy controls. Further research is needed to characterize these scleral-nerve directed antibodies and assess their clinical value.

TRPV: An emerging target in glaucoma and optic nerve damage.

Transient receptor potential vanilloid (TRPV) channels are members of the TRP channel superfamily, which are ion channels that sense mechanical and osmotic stimuli and participate in Ca2+ signalling across the cell membrane. TRPV channels play important roles in maintaining the normal functions of an organism, and defects or abnormalities in TRPV channel function cause a range of diseases, including cardiovascular, neurological and urological disorders. Glaucoma is a group of chronic progressive optic nerve diseases with pathological changes that can occur in the tissues of the anterior and posterior segments of the eye, including the ciliary body, trabecular meshwork, Schlemm's canal, and retina. TRPV channels are expressed in these tissues and play various roles in glaucoma. In this article, we review various aspects of the pathogenesis of glaucoma, the structure and function of TRPV channels, the relationship between TRPV channels and systemic diseases, and the relationship between TRPV channels and ocular diseases, especially glaucoma, and we suggest future research directions. This information will help to further our understanding of TRPV channels and provide new ideas and targets for the treatment of glaucoma and optic nerve damage.

Targeting scleral remodeling and myopia development in form deprivation myopia through inhibition of EFEMP1 expression.

The role of extracellular matrix (ECM) remodeling in the axial elongation associated with myopia has not been fully elucidated, although it is considered a significant factor. EFEMP1, a regulator of ECM, has been associated with various pathological conditions. This study aimed to examine the involvement of EFEMP1 in scleral remodeling during form deprivation myopia. The results indicate a progressive increase in EFEMP1 expression following prolonged form deprivation treatment, followed by a subsequent decrease upon recovery. To gain a deeper understanding of the mechanism of EFEMP1, we conducted transcriptome sequencing on primary scleral fibroblasts that were subjected to lentivirus-mediated overexpression of EFEMP1. Validation was performed using lentivirus-induced overexpression and shRNA targeting EFEMP1 in combination with LY294002, a PI3K inhibitor. Our findings suggest that EFEMP1 may be involved in the development of FDM by regulating the expression of the PI3K/AKT/MMP2 axis. The AAV-mediated injection of shEFEMP1 under Tenon's capsule in guinea pigs was observed to effectively delay the progression of myopia and posterior scleral remodeling. In contrast, the AAV-mediated overexpression of EFEMP1 exacerbated the development of myopia and resulted in further thinning of collagen fibers in the posterior sclera. In summary, adjusting EFEMP1 concentrations could potentially serve as a viable approach to prevent and treat myopia by influencing the remodeling process of the posterior sclera.

Scleral collagen cross linkage in progressive myopia.

High myopia is often associated with local ectasia and scleral thinning. The progression of myopia depends upon scleral biochemical and biomechanical properties. Scleral thinning is associated with decreased collagen fiber diameter, defective collagen fibrillogenesis, and collagen cross-linking. Reversing these abnormalities may make the sclera tougher and might serve as a treatment option for myopic progression. Collagen cross-linking is a natural process in the cornea and sclera, which makes the structure stiff. Exogenous collagen cross-linkage is artificially induced with the help of external mediators by using light and dark methods. In this systematic review, we discussed existing literature available on the internet on current evidence-based applications of scleral collagen cross-linking (SXL) by using different interventions. In addition, we compared them in tabular form in terms of their technique, mechanisms, cytotoxicity, and the stage of transition from preclinical to clinical development. Furthermore, we discussed the in-vivo technique to evaluate the post-SXL scleral biomechanical property and outcome in the human eye.

Fibrous finite element modeling of the optic nerve head region.

The optic nerve head (ONH) region at the posterior pole of the eye is supported by a fibrous structure of collagen fiber bundles. Discerning how the fibrous structure determines the region biomechanics is crucial to understand normal physiology, and the roles of biomechanics on vision loss. The fiber bundles within the ONH structure exhibit complex three-dimensional (3D) organization and continuity across the various tissue components. Computational models of the ONH, however, usually represent collagen fibers in a homogenized fashion without accounting for their continuity across tissues, fibers interacting with each other and other fiber-specific effects in a fibrous structure. We present a fibrous finite element (FFE) model of the ONH that incorporates discrete collagen fiber bundles and their histology-based 3D organization to study ONH biomechanics as a fibrous structure. The FFE model was constructed using polarized light microscopy data of porcine ONH cryosections, representing individual fiber bundles in the sclera, dura and pia maters with beam elements and canal tissues as continuum structures. The FFE model mimics the histological in-plane orientation and width distributions of collagen bundles as well as their continuity across different tissues. Modeling the fiber bundles as linear materials, the FFE model predicts the nonlinear ONH response observed in an inflation experiment from the literature. The model also captures important microstructural mechanisms including fiber interactions and long-range strain transmission among bundles that have not been considered before. The FFE model presented here advances our understanding of the role of fibrous collagen structure in the ONH biomechanics. STATEMENT OF SIGNIFICANCE: The microstructure and mechanics of the optic nerve head (ONH) are central to ocular physiology. Histologically, the ONH region exhibits a complex continuous fibrous structure of collagen bundles. Understanding the role of the fibrous collagen structure on ONH biomechanics requires high-fidelity computational models previously unavailable. We present a computational model of the ONH that incorporates histology-based fibrous collagen structure derived from polarized light microscopy images. The model predictions agree with experiments in the literature, and provide insight into important microstructural mechanisms of fibrous tissue biomechanics, such as long-range strain transmission along fiber bundles. Our model can be used to study the microstructural basis of biomechanical damage and the effects of collagen remodeling in glaucoma.

Posterior scleral birefringence measured by triple-input polarization-sensitive imaging as a biomarker of myopia progression.

In myopic eyes, pathological remodelling of collagen in the posterior sclera has mostly been observed ex vivo. Here we report the development of triple-input polarization-sensitive optical coherence tomography (OCT) for measuring posterior scleral birefringence. In guinea pigs and humans, the technique offers superior imaging sensitivities and accuracies than dual-input polarization-sensitive OCT. In 8-week-long studies with young guinea pigs, scleral birefringence was positively correlated with spherical equivalent refractive errors and predicted the onset of myopia. In a cross-sectional study involving adult individuals, scleral birefringence was associated with myopia status and negatively correlated with refractive errors. Triple-input polarization-sensitive OCT may help establish posterior scleral birefringence as a non-invasive biomarker for assessing the progression of myopia.

SCLERAL EXCAVATION AT OBLIQUE MUSCLE INSERTIONS: IMAGING CHARACTERISTICS AND CORRELATION WITH SCLERAL PLAQUES AND SCLEROCHOROIDAL CALCIFICATION.

PURPOSE: To compare the imaging features of lesions showing hyporeflective posterior scleral excavation found near the insertions of the oblique extraocular muscles to the features and the natural course of Cogan scleral plaques. METHODS: Multimodal imaging with color fundus photography, spectral-domain optical coherence tomography (OCT), swept-source optical coherence tomography, and B-scan ultrasonography. RESULTS: A 71-year-old man and an 89-year-old man presented with ring-shaped hypopigmented lesions measuring between 200 µm and 300 µm transversally, and located along the superior vascular arcade and temporal to the fovea. All lesions were identified near the insertion of oblique muscles, with one observed in the temporal macula, and two found along the superotemporal arcades. Enhanced depth imaging-optical coherence tomography showed hyporeflective boat-shaped areas of scleral excavation with reduced choroidal thickness along their margins. B-scan ultrasonography showed the lesions to be intensely reflective with varying degrees of posterior shadowing. CONCLUSION: To our knowledge, this is the first report of excavated hyporeflective scleral lesions found near the oblique muscle insertions. Imaging and clinical data support the diagnosis of a posterior form of Cogan scleral plaque and are consistent with the natural course of this entity.

PIGMENTATION IN FOCAL SCLERAL NODULE.

PURPOSE: To report a case of pigmentation in focal scleral nodule (FSN). METHODS: This is a single case report. RESULT: An asymptomatic 61-year-old woman was referred with small, partially pigmented raised lesion located at the superior margin of the optic nerve head. The lesion's clinical and multimodal imaging features were consistent for FSN including a dome-shaped elevation confined to the sclera with overlying choroidal thinning. However, the pigmentation within our lesion is a novel finding in FSN that has not been described before. CONCLUSION: To our knowledge, we report the first case of pigmentation in FSN. It is likely that our case was a typical FSN that then became pigmented, with melanosomes involving the flanges of the lesion where thin choroid remains. The understanding that FSN can be partially pigmented may eventually help unravel the origins of this poorly understood lesion.

A new perspective on the corneo-scleral junction with three types of microscopy techniques.

The conjunctions of the cornea and sclera in the eyes of donkeys, cattle, dogs, sheep, pigs and rabbits, regardless of gender, were examined in this study. No animals were specifically sacrificed for this investigation. Scanning electron microscopy, light microscopy, and dissecting microscopy were used in this research. In the limbus of all the animals investigated, the cornea and sclera fused in accordance with a pattern. At the corneo-scleral junction, the sclera was situated anteriorly and the cornea posteriorly in the dorsal and ventral sections of the bulbus oculi. In the medial and lateral parts of the eyeball, the cornea and sclera were facing each other and interlaced. Pigmentation and the sulcus scleralis externus could be used to identify the macro-and micro-anatomical boundaries of the limbus. In addition, the cytoplasm of basal epithelial cells shrank, signaling the end of the corneal epithelium and the start of the conjunctival epithelium. The presence of Bowman's membrane in cattle and sheep eyes was definitely determined in histological examinations. Bowman's membrane in these animals came to an end at the limbus, which is where the conjunctival epithelium starts and the corneal epithelium ends. In all areas of the cornea, Bowman's membrane revealed irregular, abrupt thickening and thinning. The corneal epithelium was thick in the vertex and thinner towards the limbus, whereas Descemet's membrane was thin in the center (vertex) and thick in the periphery (near the limbus). In this study, pictures and diagrams were used to illustrate the general anatomical, histological, and morphometric characteristics of the limbus in the species under investigation. The data from our study showed that the limbus region of the bulbus oculi was narrow in the lateral and medial parts and wide in the dorsal and ventral parts. This was confirmed in the studied animals as a general rule. The width value will undoubtedly affect the number of cells covered by the regions. It is conceivable that these cells will play a significant role in the decision of where to perform surgical procedures in order to promote wound healing, giving doctors an advantage. In this circumstances, we think that the limbus should be studied in terms of clinical methods because it has different shapes depending on the species and the position of the bulbus.

Two different procedures for managing ocular melanosis presenting scleral pigmentation with glaucoma in a Shih-Tzu dog: A case of definitive diagnosis in one eye and a presumed diagnosis in the contralateral eye.

A 12-year-old castrated male Shih-Tzu dog was referred for uncontrolled glaucoma and uveitis with highly pigmented sclera, in both eyes (OU). On ophthalmic examination, the menace response, dazzle reflex and pupillary light reflex were negative OU. The intraocular pressure was 27 mmHg in the right eye (OD) and 70 mmHg in the left eye (OS) despite the administration of antiglaucoma eyedrops. Ultrasound biomicroscopy revealed a closed ciliary cleft OU. Ocular ultrasonography revealed hyperechoic materials in the vitreous OU and retinal detachment OS. When presented for recheck, an extensive malacic corneal ulcer was observed OS. To relieve pain in the blind eyes, enucleation OS and pharmacologic ciliary body ablation (CBA) OD were performed. Histologically, ocular melanosis, which is an inherited disease in the Cairn Terrier breed, was identified in the enucleated eye. The uvea was heavily pigmented. The iris and ciliary body were mildly distorted by a single population of large, round, nonneoplastic cells with pigmented cytoplasm. There was no evidence of an intraocular mass or metastasis before and after intravitreal CBA. This is the first report of bilateral ocular melanosis in a Shih-Tzu dog. Ocular melanosis is a possible differential diagnosis for globe presenting scleral pigmentation with glaucoma in even non-Cairn Terrier breeds and pharmacologic CBA could be considered as a treatment for ocular melanosis with end-stage glaucoma.

A physical sign of pathological myopia: myopic scleral pit.

PURPOSE: Myopic scleral pit (MSP) is a rare physical sign of pathological myopia (PM). The aim of this study was to summarize the clinical characteristics of MSP and analyze its correlation with PM. METHODS: Eight cases with PM and MSP were enrolled in this study. Comprehensive ophthalmic examinations, including subjective refraction, slit-lamp biomicroscope, intraocular pressure, fundus photographs, A- and B-scan ultrasonography and spectral-domain optical coherence tomography, were performed. RESULTS: All the patients had a long history of PM with visual impairment, long axial length, and myopia-related fundus degeneration. Mean axial length was 31.48 ± 2.17 mm. Mean size of MSP was 0.69 ± 0.29 optic disc diameter (PD). Mean logMAR BCVA was 1.21 ± 0.88 logMAR. Spearman correlation analysis showed that the logMAR BCVA had no correlation with the size of pits (P = 0.34). Fundus examination revealed a focal pale concave located in the sclera exposed area of retinal choroid atrophy was found in all cases. OCT showed a deep scleral pit where the retinal choroid was thin or absent, without retinal sensory detachment or sensory defect. CONCLUSIONS: This study identified a rare scleral lesion in all eight individuals with PM, which was termed "myopic scleral pit". This phenomenon is different from focal choroidal excavation and posterior staphyloma.

Efficacy and safety of microbial transglutaminase-induced scleral stiffening invivo.

The purpose of this study was to investigate the efficacy and safety of microbial transglutaminases (mTGases) during scleral collagen cross-linking (CXL) in vivo. Sixteen New Zealand white albino rabbits were treated with sub-Tenon's injections of 2 ml of 1 U/ml mTGases in the right eye and 2 ml of phosphate buffer saline (PBS) in the left eye. The rabbits were killed 2 weeks after the injection, and all eyeballs, including some scleral strips, were processed. The elastic modulus was measured with a biomaterials tester. Histopathological analysis and transmission electron microscopy (TEM) were used for the morphological observations. The elastic modulus of the mTGase-treated sclera was 15.79 ± 2.93 MPa, and that of the control was 6.91 ± 2.23 MPa, indicating an increase of 129% after the mTGases treatment (P < 0.05). The density of the scleral collagen bundles and diameter of the collagen fibrils increased compared with those in the control group. No apoptosis was detected in the retina or posterior sclera by TUNEL staining, and no histological damage was observed on the TEM scan. This study is based on a short-term study on animal models. These results indicate that mTGase-mediated scleral CXL is a promising approach to effectively stiffen the sclera and safe enough for retina, and may be a useful treatment modality for strengthening scleral tissue.

What we know about the scleral profile and its impact on contact lens fitting.

Scleral contact lens fitting has provided practitioners with one of the earliest pieces of evidence that the sclera was more often asymmetric than symmetric. Some preliminary observations such as different haptic alignment patterns over the sclera in 360 degrees, the appearance of fogging in the fluid chamber and excessive tear out-in flow through specific meridians, quadrants, or areas of the haptic provide evidence of some scleral asymmetry. The advent of technologies that allowed measurement of the scleral profile led to formal research confirming that only about 6% of scleras are symmetric, while the rest are toric, quad-specific, or irregular. This has an evident impact on how to focus scleral lens fitting. Measuring the scleral profile also provided us with true ocular sagittal height data for cord diameters beyond the cornea. Although high variability was expected in pathological eyes, healthy eyes also showed a wide range of ocular sagittal heights. Due to this variability among healthy eyes, a discussion has emerged on whether the one-size-fits-all approach to soft lens fitting is a proper strategy to fit the whole spectrum of sagittal heights. The traditional mode of selecting the parameters for custom soft lenses through corneal parameters is also questioned.

Masquerade syndrome in ocular surface squamous neoplasia.

The aim of this study was to alert the ophthalmic community to an atypical manifestation of ocular surface squamous neoplasia, which may delay diagnosis and treatment and result in a guarded visual prognosis and significant sequelae. A 61-year-old immunocompetent man presented with an initial diagnosis of necrotizing scleritis in the right eye for 3 months. He was treated with systemic prednisone but experienced persistent pain and low visual acuity. Conjunctival biopsy of the affected region confirmed the diagnosis of invasive ocular surface squamous neoplasia, which progressed with intraocular and orbital invasion; thus, exenteration was performed. Masquerade syndrome should be suspected in patients with nodulo-ulcerative lesions of the conjunctiva and sclera. This clinical can be more aggressive, with a greater likelihood of intraocular and orbital involvement. The earlier the diagnosis and treatment, the better the patient prognosis.

Birefringence-derived scleral artifacts in optical coherence tomography images of eyes with pathologic myopia.

We investigated birefringence-derived scleral artifacts in optical coherence tomography (OCT) images of eyes with pathologic myopia. This study included 76 eyes of 42 patients with pathologic myopia. Five sets of OCT B-scan images of the macula were obtained using commercial swept-source OCT. A dataset of prototype swept-source polarization-diversity OCT images was used to identify polarization-dependent OCT images (i.e., complex averaging of OCT signals from two polarization channels) and polarization-independent OCT images (i.e., intensity averaging of two OCT signals). Polarization-dependent OCT images and commercial OCT images were assessed for the presence of birefringence-derived artifacts by comparison with polarization-independent OCT images. Both polarization-dependent OCT images and commercial OCT images contained scleral vessel artifacts. Scleral vessel artifacts were present in 46 of 76 eyes (60.5%) imaged by polarization-dependent OCT and 17 of 76 eyes (22.4%) imaged by commercial OCT. The proportion of images that showed scleral vessel artifacts was significantly greater among polarization-dependent OCT images than among commercial OCT images (P < 0.001). Additionally, polarization-dependent OCT images showed low-intensity band artifacts. This study demonstrated the existence of birefringence-derived scleral artifacts in commercial OCT images and indicated that polarization-diversity OCT is an effective tool to evaluate the presence of these artifacts.

Lrpap1 deficiency leads to myopia through TGF-ß-induced apoptosis in zebrafish.

BACKGROUND: Frameshift mutations in LRPAP1 are responsible for autosomal recessive high myopia in human beings but its underlying mechanism remains elusive. This study aims to investigate the effect of LRPAP1 defect on ocular refractive development and its involved mechanism. METHODS: A lrpap1 mutant zebrafish line with homozygous frameshift mutation was generated by CRISPR/Cas9 technology and confirmed by Sanger sequencing. The ocular refractive phenotype was analyzed by calculating the relative refractive error (RRE) with vivo photography and histological analysis at different development stages, together with examining ocular structure change via transmission electron microscopy. Further, RNA sequencing and bioinformatics analysis were performed. The potentially involved signaling pathway as well as the interacted protein were investigated in vivo. RESULTS: The lrpap1 homozygous mutant zebrafish line showed myopic phenotype. Specifically, the mutant lines showed larger eye axial length-to-body length in one-month old individuals and a myopic shift with an RRE that changed after two months. Collagen fibers became thinning and disordered in the sclera. Further, RNA sequencing and bioinformatics analysis indicated that apoptosis signaling was activated in mutant line; this was further confirmed by acridine orange and TUNEL staining. Moreover, the expression of TGF-ß protein was elevated in the mutant lines. Finally, the treatment of wild-type embryos with a TGF-ß agonist aggravated the degree of eyeball apoptosis; conversely, the use of a TGF-ß inhibitor mitigated apoptosis in mutant embryos. CONCLUSION: The study provides functional evidence of a link between lrpap1 and myopia, suggesting that lrpap1 deficiency could lead to myopia through TGF-ß-induced apoptosis signaling. Video abstract.