Temperature-dependent autoactivation associated with clinical variability of PDGFRB Asn666 substitutions.

Ocular pterygium-digital keloid dysplasia (OPDKD) presents in childhood with ingrowth of vascularized connective tissue on the cornea leading to severely reduced vision. Later the patients develop keloids on digits but are otherwise healthy. The overgrowth in OPDKD affects body parts that typically have lower temperature than 37°C. We present evidence that OPDKD is associated with a temperature sensitive, activating substitution, p.(Asn666Tyr), in PDGFRB. Phosphorylation levels of PDGFRB and downstream targets were higher in OPDKD fibroblasts at 37°C but were further greatly increased at the average corneal temperature of 32°C. This suggests that the substitution cause significant constitutive autoactivation mainly at lower temperature. In contrast, a different substitution in the same codon, p.(Asn666Ser), is associated with Penttinen type of premature aging syndrome. This devastating condition is characterized by widespread tissue degeneration, including pronounced chronic ulcers and osteolytic resorption in distal limbs. In Penttinen syndrome fibroblasts, equal and high levels of phosphorylated PDGFRB was present at both 32°C and 37°C. This indicates that this substitution causes severe constitutive autoactivation of PDGFRB regardless of temperature. In line with this, most downstream targets were not affected by lower temperature. However, STAT1, important for tissue wasting, did show further increased phosphorylation at 32°C. Temperature-dependent autoactivation offers an explanation to the strikingly different clinical outcomes of substitutions in the Asn666 codon of PDGFRB.

Inflammation and Fibrosis in Orbital Inflammatory Disease: A Histopathologic Analysis.

PURPOSE: The purpose of this study was to compare the histopathologic inflammation and fibrosis of orbital adipose tissue in orbital inflammatory disease (OID) specimens. METHODS: In this retrospective cohort study, inflammation, and fibrosis in orbital adipose tissue from patients with thyroid-associated orbitopathy (TAO), granulomatosis with polyangiitis (GPA), sarcoidosis, nonspecific orbital inflammation (NSOI), and healthy controls were scored by 2 masked ocular pathologists. Both categories were scored on a scale of 0 to 3 with scoring criteria based on the percentage of specimens containing inflammation or fibrosis, respectively. Tissue specimens were collected from oculoplastic surgeons at 8 international centers representing 4 countries. Seventy-four specimens were included: 25 with TAO, 6 with orbital GPA, 7 with orbital sarcoidosis, 24 with NSOI, and 12 healthy controls. RESULTS: The mean inflammation and fibrosis scores for healthy controls were 0.0 and 1.1, respectively. Orbital inflammatory disease groups' inflammation (I) and fibrosis (F) scores, formatted [I, F] with respective p -values when compared to controls, were: TAO [0.2, 1.4] ( p = 1, 1), GPA [1.9, 2.6] ( p = 0.003, 0.009), sarcoidosis [2.4, 1.9] ( p = 0.001, 0.023), and NSOI [1.3, 1.8] ( p ≤ 0.001, 0.018). Sarcoidosis had the highest mean inflammation score. The pairwise analysis demonstrated that sarcoidosis had a significantly higher mean inflammation score than NSOI ( p = 0.036) and TAO ( p < 0.0001), but no difference when compared to GPA. GPA had the highest mean fibrosis score, with pairwise analysis demonstrating a significantly higher mean fibrosis score than TAO ( p = 0.048). CONCLUSIONS: Mean inflammation and fibrosis scores in TAO orbital adipose tissue samples did not differ from healthy controls. In contrast, the more "intense" inflammatory diseases such as GPA, sarcoidosis, and NSOI did demonstrate higher histopathologic inflammation and fibrosis. This has implications in prognosis, therapeutic selection, and response monitoring in orbital inflammatory disease.

Periocular Pigmented Basal Cell Carcinomas: Clinicopathologic Features and Mutational Profile.

PURPOSE: Pigmented basal cell carcinomas (PBCC) is an uncommon variant of basal cell carcinoma of the periocular region with limited information in the literature. We highlight the clinicopathological profile and somatic mutations in periocular PBCC. METHODS: The clinicopathological features and somatic mutations in patients with periocular PBCC were examined and compared with periocular non-PBCC reported in the literature. Next-generation sequencing panel analysis for the excised tumors identified somatic mutations. RESULTS: In a total of 31 patients, PBCC was common in females (54%; p = 0.03); as a unilateral lower eyelid (n = 22; 71%), solitary mass (n = 30; 98%). Pathologic subtypes were variable. Most were nodular or mixed variants (n = 23; 74%). During the follow up (2.5-4.5 years), 1 patient (3.5%) had a recurrence. The clinical and pathologic features of PBCC were similar to those reported in nonperiocular locations. Somatic mutations detected in 25/31 tumors. Variants in 50/161 genes in the panel were noted. PTCH1 (14/31), TERT (12/31), and SMO (7/31) variants were common. Fifteen patients had novel drivers, including POLE, FANCD2, and CREBBP. SMO mutations were significantly more common in females (7/7), lower eyelid (5/7), and TERT mutations were more common in nodular subtype (10/12). CONCLUSIONS: In this large cohort of a relatively uncommon variant of BCC, the clinicopathological features and tumor behavior of PBCC was similar to periocular non-PBCC. The somatic mutation spectrum of PBCC resembles that reported in nonperiocular cutaneous BCC with novel drivers identified. We identified several potential actionable mutations that could be targeted with molecular therapy.

Magnitude and Determinants of Diabetic Retinopathy Among Indian Diabetic Patients Undergoing Telescreening in India.

Purpose: To determine the magnitude, determinants, and public health issues related to diabetic retinopathy (DR) in India using 2019 data from a for-profit telescreening program. Methods: Digital retinal images were captured using a nonmydriatic fundus camera and transferred via the telescreening program to a reading center. Ophthalmologists trained in DR image reading created the DR status reports. Age/sex-adjusted rates of DR, sight-threatening DR (STDR), and diabetic macular edema (DME) were calculated and correlated with known risk factors. Results: Images of 51,760 Indian diabetic patients (103,520 eyes) were reviewed. The prevalence of DR, STDR, and DME was 19.1% (95% confidence interval [CI]: 18.9-19.5), 5.1% (95% CI: 4.9-5.3), and 3.9% (95% CI: 3.7-4.1), respectively. Based on these data, we projected 14.7 million cases of DR, 3.9 million with STDR, and 3.0 million DME cases in India. Statistically significant risk factors for DR were male gender (odds ratio [OR] = 1.19, p < 0.001), older age (χ2 = 270, df = 3, p < 0.001), history of cataract surgery (OR = 2.0, p < 0.001), longer duration of diabetes (χ2 = 1084, p < 0.001), and type 1 diabetes (OR = 3.9, p = 0.01). There was a statistically significant variation of DR by geographic zones (χ2 = 310, p < 0.001). Laser treatment coverage for STDR was 22%. Duration of diabetes (p < 0.001), cataract surgery in the past (p = 0.02), and females (p = 0.001) were predictors of STDR. Conclusion: This model of telescreening for DR provides an additional pathway for screening and preventing diabetes-related visual morbidity in India. The data from this study can be used for epidemiologic and ophthalmic health policies related to diabetes.

Frequency and risk factors of narrow angles in patients with pseudoexfoliation: a case-control study.

PURPOSE: To determine the frequency and risk factors of narrow angles in pseudoexfoliation (PXF) patients. METHODS: A prospective case-control study was conducted during the period from March 2017 to December 2020. Adult patients (above 40 years) presenting with PXF were consecutively enrolled (study group). Cases were matched with individuals above 40 years presenting to a comprehensive ophthalmology clinic without evidence of PXF (control group). RESULTS: We enrolled 196 PXF patients and 98 controls. The occurrence of narrow angles was 25% in the PXF group and 5.1% in the control group (P = 0.0001). Compared to controls, PXF patients were older (72.6 ± 9.6 vs. 64.4 ± 8.5, P < 0.0001) and had a lower mean ACD (2.79 ± 0.4 vs. 3.05 ± 0.4, P < 0.0001). There was no difference in AL measurements between both groups (23.3 ± 1.4 vs. 23.7 ± 1.0, P = 0.0714). After stratification by age group and gender, the risk of narrow angles was higher in PXF patients above 70 years (OR, 4.15; 95% CI, 0.91-23.87; P, 0.044). There was no gender difference in the risk of developing narrow angles. CONCLUSION: Narrow angles are more frequently encountered in PXF patients compared to controls. Advanced age (> 70 years) is significantly associated with an increased likelihood of developing narrow angles.

Contemporary management of refractory pediatric glaucoma.

PURPOSE OF REVIEW: The management of pediatric glaucoma poses a unique challenge in terms of maintaining lifelong vision and combating an aggressive scarring response from surgery. Contemporary literature regarding the surgical management of children with pediatric glaucoma who fail, or are at a high risk of failure, from conventional surgery is limited. The aim of this review is to highlight recent developments in relation to the current opinion regarding the management of children with refractory pediatric glaucoma. RECENT FINDINGS: Some studies have reported impressive success rates with circumferential trabeculotomy, even in eyes with previous failed surgery. Early results of deep sclerectomy in populations which may not respond well to conventional angle surgery are encouraging but data is limited for the pediatric age group. In compliant patients in whom multiple postoperative examinations under anesthesia are possible, trabeculectomy remains an effective procedure. Multiple recent studies have demonstrated that glaucoma drainage device (GDD) surgery is associated with 5-year success rates of over 70% in primary childhood glaucomas. SUMMARY: Glaucoma drainage device surgery is likely to remain a mainstay of surgical management for refractory glaucoma in older children. More prospective data are needed on the success of circumferential trabeculotomy, deep sclerectomy and micropulse laser in pediatric eyes with previous failed surgery. VIDEO ABSTRACT: http://links.lww.com/COOP/A34.

Medical professionalism in ophthalmology: design and testing of a scenario based survey.

BACKGROUND: Professionalism is hard to quantify but essential in medical practice. We present a survey tool for ophthalmologists that assessed professionalism using case-based scenarios in central Saudi Arabia. METHODS: Ophthalmologists (resident, fellows and consultants) participated in a web-based survey in 2015. Out of 44 attributes related to professionalism, experts selected 32 attributes with validity indices of ≥0.80. To evaluate these attributes, 51 scenario-based questions were developed and included in the survey. For each attribute, participants were given choices of close ended responses: unacceptable (1), probably unacceptable (2), acceptable (3), probably acceptable (4). The attribute score was compared to the gold standard (responses of an expert group). An attribute score was generated and compared among subgroups. RESULTS: Of the 155 ophthalmologists, responses of 147 ophthalmologists who completed more than 50% of questions were reviewed. Their mean attribute score was 84.1 ± 10.1 (Median 87.1; 25% quartile 78.1; minimum 50; and maximum 100). The variation in attribute score among consultants, fellows and resident ophthalmologists was significant (P = 0.008). The variation of attribute score by groups of attributes was also significant (P < 0.05). The score for 'Personal characteristics' was on a lower scale compared to that of other attribute groups. The variation in the scores for attribute groups; 'Personal characteristics attribute' group (p < 0.01) and 'Workplace practices & relationship' group (P = 0.03) for consultants, fellows and residents were significant. CONCLUSIONS: Professionalism among ophthalmologists and those in training was high and influenced by years of experience. The survey tool appeared to show differences in responses to specific professional attribute groups between trainees and consultants. Additional studies with a larger sample size might be helpful in validating the survey as a tool to be used to assess professionalism in graduate medical education in ophthalmology.

Clinical and histological features and outcomes of upper eyelid colobomas in the Saudi population.

PURPOSE: To study the clinical features, histopathology, and management of congenital upper eyelid coloboma (CEC) in the Saudi population. METHODS: A retrospective review of health records evaluated the demographics, histopathology, and surgical outcomes of patients with CEC. RESULTS: Thirty-nine eyelids of 27 patients were included in this study. CEC was bilateral in 12 (44.4%) patients, isolated in 17 (62.9%), and as part of a syndrome in 10 (37.1%) patients. CEC was commonly located in the medial upper lid (22 lids, 56.4%) and mostly involved the full thickness of the lid (27 lids, 69.2%). Corneal adhesion (18 eyes, 46.1%) and poorly formed eyebrows (21 eyebrows, 53.8%) were the most common ocular/adnexa associations. Histopathology was similar in all cases and the main features were scarred dermis, atrophic orbicularis oculi, and atrophic or absent tarsus. Visual acuity at the final follow-up was 20/50 or better in 13 (33.3%) eyes. Complete lid closure without lagophthalmos after one or more surgical procedures was achieved in 11 (40.7%) cases. CONCLUSIONS: CEC features in Saudi patients are similar to those described in the literature. Dermal scarring and defective orbicularis muscles are common. Achieving cosmetic and functional success after management remains challenging.

Pathophysiology and management of glaucoma associated with phakomatoses.

The phakomatoses, encephalotrigeminal angiomatosis (ETA; Sturge-Weber Syndrome), neurofibromatosis type 1 (NF1 or von Recklinghausen disease), Von Hippel-Lindau (VHL) disease, tuberous sclerosis (TSC), oculodermal melanocytosis (ODM), and phakomatosis pigmentovascularis are a group of neurocutaneous disorders that have characteristic systemic and ocular manifestations. Through many different mechanisms, they may cause glaucomatous damage of the optic nerve and subsequent vision loss varying from mild to severe. Glaucoma commonly affects patients with ETA (43-72%), orbito-facial NF1 (23-50%), and ODM (10%). Rarely, it may present as neovascular glaucoma in VHL and TSC. In ETA, glaucoma typically occurs ipsilateral to the port-wine stain, which is caused by a mutation in the GNAQ gene. Specifically, mechanical malformation of the anterior chamber angle and elevated episcleral venous pressure has been implicated as causes of glaucoma in ETA. In NF1, which is caused by a mutation in the NF1 tumor suppressor gene, glaucoma commonly occurs ipsilateral to lid plexiform neurofibromas. Histological studies of eyes with NF1 have revealed direct anterior chamber infiltration by neurofibromas, secondary angle closure, fibrovascularization, and developmental angle abnormalities as mechanisms of glaucoma. Lastly, phakomatosis pigmentovascularis is a rare combination of ODM and port-wine stain. Affected patients are at very high risk of developing glaucoma. Despite the many different mechanisms of glaucomatous damage, management follows similar principles as that for congenital glaucoma and primary open angle glaucoma. First-line therapy is topical intraocular pressure-lowering eye drops. Surgical management, including goniotomy, trabeculotomy, trabeculectomy, and tube shunt placement may be required for more severe cases.

Anatomical differences of the protein profile in the rabbit sclera during growth.

We aimed to investigate the proteome changes in anatomical regions of sclera during growth and development of the rabbit. Sclera from New Zealand white rabbits of three ages (1 month, 2 months and 6 months) was dissected into three segments - anterior, equatorial, and posterior. A total of 36 samples were divided into groups by age and anatomical region. Tryptic digests of total proteins were analyzed by liquid chromatography followed by tandem mass spectrometry (LC-MS/MS). Label-free quantification based on spectral counts was used to determine the relative protein abundance and identify proteins with statistically significant differences between age groups or anatomical regions of the sclera. Western blotting was performed to validate some of the differentially expressed proteins. A total of 840 non-redundant proteins was identified in the sclera at different ages and regions with protein and peptide false discovery rate (FDR) at ≤1.0% and ≤0.1%, respectively. Differentially expressed proteins were identified by comparing age or anatomical region. Among these, periostin showed decreasing abundance with age, while myocilin, latent-transforming growth factor beta-binding protein 2, hyaluronan, proteoglycan link protein 1 and selenbp1 showed increasing abundance with age. In mature rabbits, alcohol dehydrogenase showed region-related differences in the sclera. Periostin showed an age-related decrease while selenbp1 showed an age-related increase in abundance in the anterior region. Vitronectin and extracellular superoxide dismutase had greater expression with age in the equatorial and posterior regions, respectively. The age related differential expression of periostin and selenbp1 was confirmed by western blotting. In conclusion, the protein profile of sclera showed age- and region-related differences. The differential protein profiles provide a baseline for understanding changes in the protein expression in the young and mature rabbit that appears to show regional changes. The changes observed in the present study add to the existing knowledge about regional alterations in biomechanical properties of sclera during growth.

OUTCOMES OF PARS PLANA VITRECTOMY IN THE MANAGEMENT OF REFRACTORY AQUEOUS MISDIRECTION SYNDROME.

PURPOSE: To determine the efficacy and complications of pars plana vitrectomy (PPV) and adjunct surgeries for aqueous misdirection refractory to medical therapy. METHODS: A retrospective review of consecutive eyes with refractory aqueous misdirection at the King Khaled Eye Specialist Hospital between 2002 and 2010. Patients underwent two-port and three-port pars plana vitrectomy (PPV) with adjunct procedures including pars plana lensectomy combined with posterior capsulectomy, hyaloido-zonulo-iridectomy, and synechiolysis. Main outcome measures included anatomical success, functional success, and factors associated with the outcomes. RESULTS: Sixty-nine eyes were evaluated over a mean follow-up period of 17.6 ± 3.8 months (3-156 months). Anatomical success was achieved in 62 eyes (90%) and functional success in 54 eyes (78%) that underwent PPV as a primary surgery. The factors associated with the altering misdirected aqueous flow and reducing intraocular pressure significantly associated with a two-line improvement of best-corrected visual acuity included surgical treatment within 4 weeks of presentation (P = 0.004) and preoperative intraocular pressure (P = 0.001). The success of two-port PPV and standard three-port PPV was similar (P = 0.7). The intraoperative and postoperative complications included retinal detachment in two eyes and endophthalmitis in one eye. CONCLUSION: The PPV was effective for managing aqueous misdirection refractory to medical therapy. Two-port or three-port PPV did not change the success rate but early surgery improved both anatomical and functional outcomes.

Congenital Sebaceous Trichofolliculoma of the Upper Eyelid.

A 6-year-old male presented with a protruding hair emerging from a temporally located nodule on his left upper eyelid 5mm above the eyelid margin since birth. The lesion was excised and sent to histopathology. The features were consistent with congenital sebaceous trichofolliculoma, a rare hamartomatous skin lesion.

Subepidermal Calcified Nodules of the Eyelid Differ in Children and Adults.

PURPOSE: Subepidermal calcified nodule of the eyelid is considered as one of the types of calcinosis cutis. It generally occurs in children, and is not known to be associated with systemic disease. The authors report histopathological and clinical findings in 14 cases of subepidermal calcified nodule of the eyelid, including 3 older patients with unique microscopic features. METHODS: Clinical records and pathological materials were critically reviewed in each case, including von kossa, CD3, CD20, and CD68 stains. RESULTS: The 14 cases presented clinically as nodular eyelid lesions. All were treated with surgical excision. The authors found 2 distinct histopathological patterns which correlated with the patients' age. In young patients, the authors observed multiple, small calcified bodies within the dermis surrounded by chronic inflammation and granulomatous foreign body reaction. On the other hand, in elderly patients, lesions were characterized by a single, large, well-demarcated amorphous calcified deposit surrounded by fibrous tissue, without chronic inflammation or foreign body reaction. One of these patients, a 70-year-old man, also suffered from gout. The presence of subepidermal calcified nodule was not documented as a preoperative diagnostic possibility in any of the cases. CONCLUSIONS: Subepidermal calcified nodule of the eyelid is a rare condition, but should be considered in any patient presenting with a painless white to yellowish colored nodule of the ocular adnexa, particularly during the teenage years. Clinicians and pathologists should be aware that this entity has a distinct appearance and could be associated with systemic conditions in elderly patients.

Defining the proteome of human iris, ciliary body, retinal pigment epithelium, and choroid.

The iris is a fine structure that controls the amount of light that enters the eye. The ciliary body controls the shape of the lens and produces aqueous humor. The retinal pigment epithelium and choroid (RPE/choroid) are essential in supporting the retina and absorbing light energy that enters the eye. Proteins were extracted from iris, ciliary body, and RPE/choroid tissues of eyes from five individuals and fractionated using SDS-PAGE. After in-gel digestion, peptides were analyzed using LC-MS/MS on an Orbitrap Elite mass spectrometer. In iris, ciliary body, and RPE/choroid, we identified 2959, 2867, and 2755 nonredundant proteins with peptide and protein false-positive rates of <0.1% and <1%, respectively. Forty-three unambiguous protein isoforms were identified in iris, ciliary body, and RPE/choroid. Four "missing proteins" were identified in ciliary body based on ≥2 proteotypic peptides. The mass spectrometric proteome database of the human iris, ciliary body, and RPE/choroid may serve as a valuable resource for future investigations of the eye in health and disease. The MS proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifiers PXD001424 and PXD002194.

Spectral-domain optical coherence tomography reveals prelaminar membranes in optic nerve head pallor in eyes with retinitis pigmentosa.

PURPOSE: To determine the relationship between prelaminar structural changes of the optic nerve head (ONH) and optic nerve waxy pallor in retinitis pigmentosa (RP) using spectral-domain optical coherence tomography (SD-OCT) and fundus photography. METHODS: An observational cross-sectional case control study of patients with RP with and without ONH waxy pallor and controls. Subjects underwent clinical examination, fundus photography, and SD-OCT raster imaging of the ONH. Four independent specialists reviewed the images in a masked fashion. RESULTS: Fifty-five eyes of 31 subjects with RP and 28 eyes of 14 controls were included. Optic nerve head waxy pallor was seen in 29 RP eyes (52.7 %) and none in controls. SD-OCT showed a hyper-reflective structure suggestive of a glial membrane-like structure on the surface of ONH in 16 of RP eyes (55.1 %). In the RP group, there was a significant positive correlation between the ONH pallor and the presence of a prelaminar structure (p = 0.006). CONCLUSIONS: There is a presence of glial membrane-like structures on the optic nerve head surface in eyes with RP compared to healthy eyes. As the presence of glial membranes correlated with the presence of ONH waxy pallor, in such cases these membranes might be responsible for ONH waxy pallor.

Causes of elevated intraocular pressure following implantation of phakic intraocular lenses for myopia.

The purpose of this study is to present the causes and visual acuity outcomes in patients with elevated intraocular pressure (IOP) following implantable collamer lens (ICL) implantation. A chart review identified patients who developed high IOP at any postoperative examination and a minimum follow-up period of 3 months after ICL implantation. Data are reported out to 6 months postoperatively. Outcome measures included causes of elevated IOP, best-corrected visual acuity (BCVA) at last visit, number of glaucoma medications, other interventions, and glaucomatous damage. Elevated IOP occurred in 58 (10.8 %) of 534 eyes that received ICL. The mean age was 28 ± 7.2 years. The preoperative IOP was 16.3 ± 1.2 mmHg. Elevated IOP most commonly occurred on the first postoperative day (23/58 (39.7 %) eyes) due to retained viscoelastic. This was followed by steroid response in 22/58 (37.9 %) eyes at 2-4 weeks postoperatively. IOP elevation in 6 (10.3 %) eyes was related to high ICL vault and pupillary block, and in 4 (6.9 %) eyes due to synechial angle closure. At last visit, BCVA was 20/40 or better in 56/58 (96.6 %) eyes, and 5/58 (8.6 %) eyes remained on glaucoma medications due to persistent steroid response (2 eyes), synechial angle closure glaucoma (1 eye), and other causes (2 eyes). One eye showed glaucomatous damage. Two eyes with high vault and elevated IOP underwent ICL explantation. There is a moderate risk of transiently developing elevated IOP after ICL implantation. Thorough removal of viscoelastic and use of anti-glaucoma medications during steroid use will reduce the majority of cases with postoperative IOP elevation.

Orbital pseudotumor can be a localized form of granulomatosis with polyangiitis as revealed by gene expression profiling.

Biopsies and ANCA testing for limited forms of granulomatosis with polyangiitis (GPA) are frequently non-diagnostic. We characterized gene expression in GPA and other causes of orbital inflammation. We tested the hypothesis that a sub-set of patients with non-specific orbital inflammation (NSOI, also known as pseudotumor) mimics a limited form of GPA. Formalin-fixed, paraffin-embedded orbital biopsies were obtained from controls (n=20) and patients with GPA (n=6), NSOI (n=25), sarcoidosis (n=7), or thyroid eye disease (TED) (n=20) and were divided into discovery and validation sets. Transcripts in the tissues were quantified using Affymetrix U133 Plus 2.0 microarrays. Distinct gene expression profiles for controls and subjects with GPA, TED, or sarcoidosis were evident by principal coordinate analyses. Compared with healthy controls, 285 probe sets had elevated signals in subjects with GPA and 1472 were decreased (>1.5-fold difference, false discovery rate adjusted p<0.05). The immunoglobulin family of genes had the most dramatic increase in expression. Although gene expression in GPA could be readily distinguished from gene expression in TED, sarcoidosis, or controls, a comparison of gene expression in GPA versus NSOI found no statistically significant differences. Thus, forms of orbital inflammation can be distinguished based on gene expression. NSOI/pseudotumor is heterogeneous but often may be an unrecognized, localized form of GPA.

Magnetic resonance imaging of uveitis.

INTRODUCTION: Uveitis is a term used to describe inflammation of the choroid, iris, or ciliary body, which make up the uveal tract. It can be idiopathic or associated with a systemic disease which may be infectious or noninfectious. With the exception of B-scan ultrasonography, current imaging methods for diagnosing and monitoring uveitis are predominately non-radiologic. Although MRI has been anecdotally shown to detect various inflammatory conditions of the globe, such as posterior scleritis, endophthalmitis, and posterior uveitis secondary to Vogt-Koyanagi-Harada disease, a more comprehensive review of the MRI findings in uveitis of various etiologies is presented here. METHODS: The MRI and CT studies of seven patients with uveitis and the clinical history of three of them (not available in four patients) were reviewed. Etiologies included ankylosing spondylitis, relapsing polychondritis, Vogt-Koyanagi-Harada disease, sarcoidosis, and tuberculosis. RESULTS: Increased gadolinium enhancement of the uveal tract, which is visualized as the enhancing layer immediately deep to the low-signal sclera, was seen on all six MRI studies. Diffusion-weighted imaging of a case with posterior uveitis and subretinal effusions revealed restriction within the uvea and effusions. Two patients had inflammatory nodules adherent to the uvea, two patients had vitreous humor abnormalities, and one patient exhibited proximal perineural and perimuscular spread of enhancement. Uveoscleral thickening and enhancement with a posterior calcification were observed in the patient with chronic uveitis imaged with CT. CONCLUSIONS: Increased uveal tract enhancement is a common finding in patients with uveitis, regardless of anatomic distribution and etiology. MRI can also further evaluate complications of uveitis and help differentiate it from masquerade syndromes.

Comparative integrated molecular analysis of intraocular medulloepitheliomas and central nervous system embryonal tumors with multilayered rosettes confirms that they are distinct nosologic entities.

Intraocular medulloepithelioma (IO MEPL) is an uncommon embryonal neuroepithelial neoplasm of the eye. These ocular neoplasms have been compared with intracranial medulloepitheliomas or other histologic variants of CNS embryonal tumor with multilayered rosettes (CNS ETMR) due to their morphological mimicry. We performed comprehensive molecular analysis to explore the histogenetic and biologic relationships between 22 IO MEPL and 68 CNS ETMR. Routinely prepared paraffin-embedded samples were assessed for genome-wide methylation profiles using the Illumina Methylation 450k BeadChip array. We identified strong cytogenetic and epigenetic differences between ocular neoplasms and CNS ETMR. None of the IO MEPL cases displayed the ETMR-specific amplification of the C19MC locus. Instead, cytogenetic analysis of the IO MEPL showed numerous copy number aberrations which involved either whole chromosomes or chromosomal arms; recurrent aberrations in these tumors affected chromosomes 1p, 4, 8 and 16p. DNA methylation patterns were also strikingly different between these two tumor entities, suggesting that they do not share common origins and biological behaviors. Comparative cluster analysis of 198 pediatric CNS tumors and 22 IO MEPL revealed a clear demarcation of the CNS ETMR and IO MEPL profiles from other CNS entities. In conclusion, although IO MEPL shares some histopathological features with CNS ETMR, they manifest striking molecular diversity at the cytogenetic and epigenetic levels. Consequently they deserve a separate nosologic designation in future tumor classifications, where CNS MEPL could be designated as a histological variant of CNS ETMR.

Clinical and Optical Coherence Tomography Correlation of Recurrence Patterns After Femtosecond Laser-Assisted Anterior Lamellar Keratoplasty in Reis-Bucklers Corneal Dystrophy.

PURPOSE: The aim of this study was to report the clinical profile and patterns of recurrence after femtosecond laser-assisted anterior lamellar keratoplasty (FALK) in Reis-Bucklers corneal dystrophy. METHODS: This is a case series of 5 eyes of 4 patients with Reis-Bucklers corneal dystrophy. Clinical images of recurrence were correlated with the high-resolution optical coherence tomography. Histopathologic examination of excised corneal samples was performed when possible. RESULTS: The median time to recurrence was 2 (1-5) years after FALK. Of the 5 eyes, 1 eye had primary FALK, whereas 4 eyes had secondary interventions, which included previous phototherapeutic keratectomy (once in 1 eye and twice in 2 eyes), and previous penetrating keratoplasty, followed by phototherapeutic keratectomy (1 eye). Recurrence was noted at the level of the subepithelium. In addition, 1 eye showed interface deposits along with epithelial downgrowth at the graft-host bed. CONCLUSIONS: The 2 distinct patterns of recurrence noted were at the subepithelial region and the interface. The clinical patterns of recurrence favor an epithelial origin of recurrent deposits.