Search

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.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.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).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.

Purpose To evaluate the outcomes of orbital hydrogel expanders in the management of congenital anophthalmia. Methods In this retrospective one-armed cohort study, a chart review was performed of eight children with congenital anophthalmia who underwent orbital expansion using orbital hydrogel tissue expander from January 2006 to July 2018. Computed tomography (CT) of orbital parameters was evaluated before and after surgery. Changes in the orbital parameters were correlated with clinical factors. Results The study sample comprised 11 anophthalmic orbits of eight children (seven males, one female; median age = 12 months), with a median postoperative follow-up of 3.8 years. The anophthalmic orbital parameters after hydrogel expander implantation improved significantly compared to preoperative assessment as follows: mean orbital height improved from 21.7 mm to 25.4 mm (P Conclusions Orbital hydrogel expander can improve the orbital development in congenital anophthalmia. However, the enlargement is not as extensive as that observed in the normal orbit. Orbital expanders associated with external conformers were not sufficient to induce normal growth of lids and fornix.

Purpose: To assess the prognostic values of the T classification of the 8th edition of the American Joint Committee of Cancer staging system and compare it to the 7th edition. Methods: Multicenter retrospective study of patients with eyelid sebaceous gland carcinoma. The primary outcome measure was the differences between outcomes when tumors were staged with either 7th or 8th edition. The measures evaluated included presenting features, management, histopathology, metastasis, recurrence, and mortality. Results: Of the 60 patients (median age 73 years), 31 (51.7%) were females. A change in T staging occurred in 39 patients (65%) when the 8th edition was applied. Advanced categories (T3/T4) were significantly associated with nodal metastasis ( p = 0.037) using the 8th edition criteria but not with the 7th edition ( p = 0.066). The 8th edition T categorization significantly correlated with eye survival ( p = 0.022) while the 7th edition did not ( p = 0.058). Applying the 8th edition, category T4 at presentation was associated with a higher risk of nodal metastasis ( p = 0.037) but not associated with local recurrence, distant metastasis, or tumor-related death ( p = 0.281, p = 0.737, p = 0.319, respectively). T3/T4 category tumors were significantly associated with poor tumor differentiation ( p = 0.001), and papillary histologic pattern ( p = 0.024) but not with pagetoid spread ( p = 0.056). Conclusion: The application of the 8th edition AJCC staging system for eyelid SGC may accurately predict nodal metastasis. Local recurrence and distant metastasis were not significantly associated with T classification, using either edition. Poor tumor differentiation and papillary pattern were associated with T3/T4 categories suggesting that pathological features may assist in determining prognosis.

Purpose Programmed cell death protein 1 (PD-1) and DNA mismatch repair (MMR) deficiency play an important role in tumour progression and response to treatment. Both markers have been studied in some ocular tumours but little is known about these markers in orbital tumours. This pilot study reports on PD-L1 expression and MMR mutations using next generation sequencing (NGS) in specific orbital tumours. Methods We reviewed surgical specimens from patients with rhabdomyosarcoma, adenoid cystic carcinoma (ACC), pleomorphic adenoma (PA) and biopsy negative tissue from orbital tumours used as a control. immunohistochemistry (IHC) was performed on Formalin fixed paraffin embedded tissue using a PD-L1 antibody. DNA was extracted for targeted gene panel NGS of the MMR genes PMS2, MLH1, MSH6 and MSH2. Results The study included 17 orbital specimens. Scattered membrane PD-L1 staining was noted in 3/6 rhabdomyosarcoma specimens without an accompanying lymphocytic infiltrate. PD-L1 immunostaining was absent in 3/3 ACC, and 5/6 PA specimens. PD-L1 immunostaining was not detected in 2/2 control specimens. 4/17 samples shared the same pathogenic mutation in the MLH1 gene, including 3/6 rhabdomyosarcoma and 1/3 ACC samples. 1/6 PA samples had a mutation in MSH6. Conclusions Our study demonstrated scattered, non-quantifiable or absent PD-L1 staining in a limited sample of orbital tumours suggesting that PD-1/PD-L1 inhibitor therapy may not be useful in treatment of malignant orbital tumours (rhabdomyosarcoma and ACC) when refractory to conventional therapy. Our pilot study suggest that PD-L1/MMR axis might not play a major role in the pathogenesis of primary orbital tumour.

Although most commonly benign, neurofibromas (NFs) can have devastating functional and cosmetic effects in addition to the possibility of malignant transformation. Orbitofacial NFs, in particular, may cause progressive, disfiguring tumors of the lid, brow, temple, face, and orbit, and clinical evidence suggests that they may have increased local aggressiveness compared to NFs developing at other sites. The purpose of this study was to identify biological differences between orbitofacial NFs and those occurring at other anatomic sites. We performed RNA‐sequencing in orbitofacial (n = 10) and non‐orbitofacial (n = 9) NFs. Differential gene expression analysis demonstrated that a variety of gene sets including genes involved in cell proliferation, interferon, and immune‐related pathways were enriched in orbitofacial NF. Comparisons with publicly available databases of various Schwann cell tumors and malignant peripheral nerve sheath tumor (MPNST) revealed a significant overlap of differentially expressed genes between orbitofacial versus non‐orbitofacial NF and plexiform NF versus MPNST. In summary, we identified gene expression differences between orbitofacial NF and NFs occurring at other locations. Further investigation may be warranted, given that orbitofacial NF are notoriously difficult to treat and associated with disproportionate morbidity., Global gene expression differences between orbitofacial neurofibromas and neurofibromas occurring at other anatomic locations were deteted through RNA sequencing analysis. Differences in pathways involved in cell cycle and inflammation were specifically detected through gene enrichment analyses, supporting prior clinical observations suggesting that orbitofacial neurofibromas are biologically distinct compared to neurofibromas developing in other anatomical sites.

Neurothekeoma (NTK) is a specific benign soft tissue tumor, typically involving the skin of the head and neck area as well as the upper part of the body in young age with female predominance. It has a typical lobular pattern of growth but often displays atypical features such as myxoid stroma or fascicular pattern, which makes the diagnosis more difficult and may necessitate the use of immunohistochemical staining to differentiate NTK from nerve sheath tumor. Ocular NTK in general is very rare with only 11 cases previously reported. We are presenting a case of recurrent mixed cellular/myxoid NTK involving the lateral canthal area of a 16-year-old-boy and we demonstrate the diagnostic challenge in such cases to attract the attention of ophthalmologists and pathologist to the rare occurrence of NTK in the ocular region.

We describe a diabetic patient with left eye endogenous endophthalmitis due to hypervirulent hypermucoviscous Klebsiella pneumoniae (HKVP) originating from right renal abscesses. A rare source of HVKP causing endogenous endophthalmitis. Despite treatment with intravenous ceftazidime and pars plana vitrectomy, the patient required evisceration of the left eye. A high index of suspicion for endogenous endophthalmitis and awareness of the virulence and potential antibiotic resistance of HVKP strains in the community is needed to avoid vision and life-threatening consequences.

To evaluate and compare the clinical and histopathological profile of primary and recurrent orbital-periorbital plexiform neurofibromas (OPPN) in patients with neurofibromatosis type 1. We retrospectively evaluated 43 primary or recurrent neurofibroma (NF) specimens from 26 patients (2002 to 2018) at the King Khaled Eye Specialist Hospital, Saudi Arabia. Demographics, clinical presentation, and surgical intervention data were collected. Histopathological specimens were studied with hematoxylin-eosin, Alcian blue, and immunohistochemical markers; S-100, CD44, CD117, smooth muscle actin (SMA), neurofilament, and Ki-67. Of the 43 NFs specimens, 20 were primary and 23 recurrent tumors. For primary NF, the ratio of plexiform to the diffuse type was 13:7, however in recurrent tumors was 3:8 after the first recurrence, and 1:5 after multiple recurrences. Of the 17 patients with primary tumors that had paired recurrent tumors, 12/17 (70.6%) primary NFs were plexiform and 5/17 (29.4%) were diffuse. However, when tumors recurred, 13/17 tumors (76.5%) were diffuse and only 4/17 tumors (23.5%) had a plexiform pattern. The odds of a tumor having a diffuse pattern in recurrent NF was significantly higher than the plexiform pattern [OR = 7.8 (95% confidence interval 1.69:36.1) P = 0.008]. Primary plexiform NFs underwent an excision at a significantly younger age than the diffuse type. Recurrent NFs had significantly higher CD44, CD117, and neurofilament labeling (P = 0.02, P = 0.01 and P.001 respectively) but had significantly decreased Alcian blue, and S-100 labeling (P = 0.03, and P = 0.02 respectively) compared to primary tumors. SMA and Ki-67 proliferation index were not different between primary and recurrent NFs (P = 0.86, and P = 0.3 respectively). There appears to be a high risk for primary plexiform NFs to develop a diffuse histologic pattern when they recur. Immunohistochemical staining suggests a role of mast cells (CD117) and expression of infiltration makers (CD44) in the transformation of plexiform tumors to the diffuse phenotype.

Although most commonly benign, neurofibromas (NFs) can have devastating functional and cosmetic effects in addition to the possibility of malignant transformation. Orbitofacial NFs in particular may cause progressive, disfiguring tumors of the lid, brow, temple, face and orbit, and anecdotal evidence suggest that they may have increased local aggressiveness compared to NFs developing at other sites. The purpose of this study was to identify biological differences between orbitofacial NFs and those occurring at other anatomic sites. We performed global RNA-sequencing in orbitofacial (n=10) and non-orbitofacial (n=9) NFs. A total of 880 mRNA transcripts were differentially expressed between the two groups (adjusted p>0.05), The top 10 genes relatively overexpressed in orbitofacial NF included NEFL, TREM2, CST1, GAP43, ADORA3, MIA, SYT6, FCGR3A, SPP1, and FCGR1A. The top 10 genes relatively underexpressed in orbitofacial NF included XG, WISP2, MMP27, CXCL14, MFAP5, APLNR, MYOC, SLITRK6, STMN2, and TDRD1. Gene enrichment analyses demonstrated a variety of gene sets differentially affected including pathways involved in cell proliferation, interferon and immune related pathways. Comparisons with publicly available databases of various Schwann cell tumors and models using CAT plots demonstrated the highest overlap with differentially expressed genes in plexiform NF vs MPNST (>10%). In summary, we identified gene expression differences between orbitofacial NF and NFs occurring at other anatomic locations. Further investigation may be warranted, given that orbitofacial NF are notoriously difficult to treat and associated with disproportionate morbidity. Citation Format: Eddie L. Imada, Deepak P. Edward, Antje Arnold, Hailah Al-Hussain, Diego Strianese, Luigi Marchionni, Fausto J. Rodriguez. Gene expression analysis by RNA-sequencing highlights differential regulated pathways involved in cell cycle and inflammation in orbitofacial neurofibromas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2251.

Conjunctival squamous cell carcinoma is a malignancy of the ocular surface. The molecular drivers responsible for the development and progression of this disease are not well understood. We therefore compared the transcriptional profiles of eight snap-frozen conjunctival squamous cell carcinomas and one in situ lesion with normal conjunctival specimens in order to identify diagnostic markers or therapeutic targets. RNA was analyzed using oligonucleotide microarrays, and a wide range of transcripts with altered expression identified, including many dysregulated in carcinomas arising at other sites. Among the upregulated genes, we observed more than 30-fold induction of the matrix metalloproteinases, MMP-9 and MMP-11, as well as a prominent increase in the mRNA level of a calcium-binding protein important for the intracellular calcium signaling, S100A2, which was induced over 20-fold in the tumor cohort. Clusterin was the most downregulated gene, with an approximately 180-fold reduction in the mRNA expression. These alterations were all confirmed by qPCR in the samples used for initial microarray analysis. In addition, immunohistochemical analysis confirmed the overexpression of MMP-11 and S100A2, as well as reductions in clusterin, in several independent in situ carcinomas of conjunctiva. These data identify a number of alterations, including upregulation of MMP-9, MMP-11, and S100A2, as well as downregulation of clusterin, associated with epithelial tumorigenesis in the ocular surface.

Little is known about the molecular alterations that drive formation and growth of conjunctival squamous cell carcinoma (cSCC). We therefore sought to identify genetic changes that could be used as diagnostic markers or therapeutic targets.The DNA extracted from 10 snap-frozen cSCC tumor specimens and 2 in situ carcinomas was analyzed using array-based comparative genomic hybridization (aCGH), and further examined with NanoString and quantitative PCR.The number of regions of DNA loss ranged from 1 to 23 per tumor, whereas gains and amplifications ranged from 1 to 15 per tumor. Most large regions of chromosomal gain and loss were confirmed by NanoString karyotype analysis. The commonest alteration was amplification of 8p11.22 in 9 tumors (75%), and quantitative PCR analysis revealed 100-fold or greater overexpression of ADAM3A mRNA from 8p11.22 locus. In addition, recurring losses were observed at 14q13.2 and 22q11.23, both lost in 5 (42%) of the 12 tumors, and at 12p13.31, lost in 4 (33%) of the 12 samples. Of the eight loci associated with the DNA damage repair syndrome xeroderma pigmentosum, three showed loss of at least one allele in our aCGH analysis, including XPA (9q22.33, one tumor), XPE/DDB2 (11p11.2, one tumor) and XPG/ERCC5 (13q33.1, three tumors).Conjunctival SCC contains a range of chromosomal alterations potentially important in tumor formation and growth. Amplification of 8p11.22 and overexpression of ADAM3A suggests a potential role for this protease. Our findings also suggest that defects in DNA repair loci are important in sporadic cSCC.

Purpose: To describe six cases of anterior orbital and adnexal amyloidosis and to report on proteomic analysis to characterize the nature of amyloid in archived biopsies in two cases. Materials and Methods: The clinical features, radiological findings, pathology, and outcome of six patients with anterior orbit and adnexal amyloidosis were retrieved from the medical records. The biochemical nature of the amyloid was determined using liquid chromatography/mass spectroscopy archived paraffin-embedded tissue in two cases. Results: Of the six cases, three had unilateral localized anterior orbit and lacrimal gland involvement. Four of the six patients were female with an average duration of 12.8 years from the time of onset to presentation eyelid infiltration by amyloid caused ptosis in five cases. CT scan in patients with lacrimal gland involvement ( n = 3) demonstrated calcified deformable anterior orbital masses and on pathological exmaintionamyloid and calcific deposits replaced the lacrimal gland acini. Ptosis repair was performed in three patients with good outcomes. One patient required repeated debulking of the mass and one patient had recurrenct disease. Proteomic analysis revealed polyclonal IgG-associated amyloid deposition in one patient and AL kappa amyloid in the second patient. Conclusion: Amyloidosis of the anterior orbit and lacrimal gland can present with a wide spectrum of findings with good outcomes after surgical excision. The nature of amyloid material can be precisely determined in archival pathology blocks using diagnostic proteomic analysis.

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

To clarify the pathogenesis of fibrosis in inflammatory orbital diseases, we analysed the gene expression in orbital biopsies and compared our results with those reported for idiopathic pulmonary fibrosis.We collected 140 biopsies from 138 patients (58 lacrimal glands; 82 orbital fat). Diagnoses included healthy controls (n=27), non-specific orbital inflammation (NSOI) (n=61), thyroid eye disease (TED) (n=29), sarcoidosis (n=14) and granulomatosis with polyangiitis (GPA) (n=7). Fibrosis was scored on a 0-3 scale by two experts, ophthalmic pathologists. Gene expression was quantified using Affymetrix U133 plus 2.0 microarray.Within orbital fat, fibrosis was greatest among subjects with GPA (2.75±0.46) and significantly increased in tissue from subjects with GPA, NSOI or sarcoidosis (p0.01), but not for TED, compared with healthy controls (1.13±0.69). For lacrimal gland, the average score among controls (1.36±0.48) did not differ statistically from any of the four disease groups. Seventy-three probe sets identified transcripts correlating with fibrosis in orbital fat (false discovery rate0.05) after accounting for batch effects, disease type, age and sex. Transcripts with increased expression included fibronectin, lumican, thrombospondin and collagen types I and VIII, each of which has been reported upregulated in pulmonary fibrosis.A pathologist's recognition of fibrosis in orbital tissue correlates well with increased expression of transcripts that are considered essential in fibrosis. Many transcripts implicated in orbital fibrosis have been previously implicated in pulmonary fibrosis. TED differs from other causes of orbital fat inflammation because fibrosis is not a major component. Marked fibrosis is less common in the lacrimal gland compared with orbital adipose tissue.

Background Although thyroid eye disease is a common complication of Graves' disease, the pathogenesis of the orbital disease is poorly understood. Most authorities implicate the immune response as an important causal factor. We sought to clarify pathogenesis by using gene expression microarray. Methods An international consortium of ocular pathologists and orbital surgeons contributed formalin fixed orbital biopsies. RNA was extracted from orbital tissue from 20 healthy controls, 25 patients with thyroid eye disease (TED), 25 patients with nonspecific orbital inflammation (NSOI), 7 patients with sarcoidosis and 6 patients with granulomatosis with polyangiitis (GPA). Tissue was divided into a discovery set and a validation set. Gene expression was quantified using Affymetrix U133 Plus 2.0 microarrays which include 54,000 probe sets. Results Principal component analysis showed that gene expression from tissue from patients with TED more closely resembled gene expression from healthy control tissue in comparison to gene expression characteristic of sarcoidosis, NSOI, or granulomatosis with polyangiitis. Unsupervised cluster dendrograms further indicated the similarity between TED and healthy controls. Heat maps based on gene expression for cytokines, chemokines, or their receptors showed that these inflammatory markers were associated with NSOI, sarcoidosis, or GPA much more frequently than with TED. Conclusion This is the first study to compare gene expression in TED to gene expression associated with other causes of exophthalmos. The juxtaposition shows that inflammatory markers are far less characteristic of TED relative to other orbital inflammatory diseases.

Objective IgG4-related disease is an emerging clinical entity which frequently involves tissue within the orbit. In order to appreciate the implications of IgG4 immunostaining, we analyzed gene expression and the prevalence of IgG4- immunostaining among subjects with orbital inflammatory diseases. Methods We organized an international consortium to collect orbital biopsies from 108 subjects including 22 with no known orbital disease, 42 with nonspecific orbital inflammatory disease (NSOI), 26 with thyroid eye disease (TED), 12 with sarcoidosis, and 6 with granulomatosis with polyangiitis (GPA). Lacrimal gland and orbital adipose tissue biopsies were immunostained for IgG4 or IgG secreting plasma cells. RNA transcripts were quantified by Affymetrix arrays. Results None of the healthy controls or subjects with TED had substantial IgG4 staining. Among the 63 others, the prevalence of significant IgG4-immunostaining ranged from 11 to 39% depending on the definition for significant. IgG4 staining was detectable in the majority of tissues from subjects with GPA and less commonly in tissue from subjects with sarcoidosis or NSOI. The detection of IgG4+ cells correlated with inflammation in the lacrimal gland based on histology. IgG4 staining tissue expressed an increase in transcripts associated with inflammation, especially B cell-related genes. Functional annotation analysis confirmed this. Conclusion IgG4+ plasma cells are common in orbital tissue from patients with sarcoidosis, GPA, or NSOI. Even using the low threshold of 10 IgG4+ cells/high powered field, IgG4 staining correlates with increased inflammation in the lacrimal gland based on histology and gene expression.

Two patients with extruded implants postevisceration were assessed and managed with room temperature vulcanized (RTV) silicone implants placed in the retroscleral-intraconal space. The technique described is an alternative and simple surgical method that provides utilization of the remaining sclera, anterior support for the implant, and adequate volume replacement. The postoperative follow-up is relatively short, and clinical and radiologic (CT scan) investigations support the efficacy of the procedure. To the best of our knowledge, such a surgical alternative has not been reported.

Purpose: To study the clinical profile of Saudi cases of xeroderma pigmentosum (XP). Design: This is a single-center, retrospective, consecutive case series of all cases of XP seen at King Khaled Eye Specialist Hospital from January 1, 1986, to December 31, 2006. The main outcome measures were clinical features, visual outcome, and histopathologic findings. Results: Of 33 patients initially included in this study, 6 were excluded from the final analysis because of either unconfirmed diagnosis of XP or insufficient follow up. The final analysis included 27 patients (14 female patients, 13 male patients). A history of consanguinity was present in the parents of one third of our patients. The age at onset of ocular complications ranged from 5 to 67 years (median age, 19 years). The number of patients with no light perception (NLP) increased from 1 patient (3.7%) at the initial visit to 5 patients (18.5%) at the last visit. In 13 of 27 patients (48.1%), conjunctival tumors were observed; 10 tumors were confirmed histopathologically to be squamous cell carcinomas. Basal cell carcinoma (BCC) was the most common histopathologic diagnosis of eyelid tumors and was noted in 4 patients (14.8%). Furthermore, 10 patients (37.0%) had a history of skin malignancy, and 5 patients (18.1%) had neurologic abnormalities. Conclusion: Patients with XP who presented to a tertiary eye care center in Saudi Arabia had a high percentage of consanguinity in parents and late onset of ocular complications. Additionally, XP behaved aggressively in both malignancy profile and visual outcome.

Congenital nasolacrimal duct (NLD) obstruction, the most common cause of congenital epiphora, occurs in approximately 5% of newborns. Before the advent of canaliculodacryo intubation, management of most cases of partial lacrimal obstruction that failed conservative management and probing necessitated bypass surgery such as dacryocystorhinostomy. Noninvasive closed system lacrimal intubation improved the success rate and provided a non-surgical therapeutic alternative. We present 129 eyes with congenital NLD obstruction managed with silastic lacrimal intubations. Early management is recommended with a minimum of 7 months' retention of the stents. Statistical assessment of results and management of complications is presented.

Objective Medulloepithelioma is a rare intraocular embryonal neuroepithelial tumour. The study aims at identifying the causes for the delay in diagnosis and treatment. Design A retrospective study of all cases with histopathologic diagnosis of medulloepithelioma over a period of 25 years. Participants Six patients with intraocular tumour in 6 eyes. Methods A data collection sheet is used for clinical and radiologic information based on charts review. The histologic sections are reviewed by a single pathologist. Results All cases presented initially in childhood with equal sex distribution. There was a delay of up to 5 years until final diagnosis and management. The most common clinical findings were high intraocular pressure and/or cataract in 4 cases, visible mass/uveitis/iris neovascularization and buphthalmos each presenting in 50% of the patients. The diagnosis was established clinically in 2 cased and by ultrasound in 4 cases. The tumour was mostly malignant (4/6) and 2 cases were classified as teratoid (1 benign and 1 malignant). All patients were successfully treated by enucleation with a follow-up period up to 18 years. Conclusions Medulloepithelioma is a rare intraocular tumour often misdiagnosed and treated as glaucoma or uveitis. Ultrasonography is a useful additional tool for diagnosis. Enucleation seems to be an appropriate method of treatment specially when diagnosis is delayed and malignancy is suspected. Ophthalmologists need to be more familiar with this tumour to allow early clinical recognition and diagnosis.

Importance Sarcoidosis is a major cause of ocular or periocular inflammation. The pathogenesis of sarcoidosis is incompletely understood and diagnosis often requires a biopsy. Objective To determine how gene expression in either orbital adipose tissue or the lacrimal gland affected by sarcoidosis compares with gene expression in other causes of orbital disease and how gene expression in tissue affected by sarcoidosis compares with gene expression in peripheral blood samples obtained from patients with sarcoidosis. Design, Setting, and Participants In a multicenter, international, observational study, gene expression profiling of formalin-fixed biopsy specimens, using GeneChipp U133 Plus 2 microarrays (Affymetrix), was conducted between October 2012 and January 2014 on tissues biopsied from January 2000 through June 2013. Participants included 12 patients with orbital sarcoidosis (7 in adipose tissue; 5 affecting the lacrimal gland) as well as comparable tissue from 6 healthy individuals serving as controls or patients with thyroid eye disease, nonspecific orbital inflammation, or granulomatosis with polyangiitis. In addition, results were compared with gene expression in peripheral blood samples obtained from 12 historical individuals with sarcoidosis. Main Outcomes and Measures Significantly differentially expressed transcripts defined as a minimum of a 1.5-fold increase or a comparable decrease and a false discovery rate of P Results Signals from 2449 probe sets (transcripts from approximately 1522 genes) were significantly increased in the orbital adipose tissue from patients with sarcoidosis. Signals from 4050 probe sets (approximately 2619 genes) were significantly decreased. Signals from 3069 probe sets (approximately 2001 genes) were significantly higher and 3320 (approximately 2283 genes) were significantly lower in the lacrimal gland for patients with sarcoidosis. Ninety-two probe sets (approximately 69 genes) had significantly elevated signals and 67 probe sets (approximately 56 genes) had significantly lower signals in both orbital tissues and in peripheral blood from patients with sarcoidosis. The transcription factors, interferon-response factor 1, interferon-response factor 2, and nuclear factor κB, were strongly implicated in the expression of messenger RNA upregulated in common in the 3 tissues. Conclusions and Relevance Gene expression in sarcoidosis involving the orbit or lacrimal gland can be distinguished from gene expression patterns in control tissue and overlaps with many transcripts upregulated or downregulated in the peripheral blood of patients with sarcoidosis. These observations suggest that common pathogenic mechanisms contribute to sarcoidosis in different sites. The observations support the hypothesis that a pattern of gene expression profiles could provide diagnostic information in patients with sarcoidosis.

The brittle cornea syndrome (BCS) is a generalized connective tissue disorder characterized by corneal rupture following only minor trauma, keratoconus or keratoglobus, blue sclerae, hyperelasticity of the skin without excessive fragility, and hypermobility of the joints. It is inherited as an autosomal recessive trait but the underlying genetic defect remains undetermined. We present 23 patients (11 male) from 13 nuclear families followed at the King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia, aged 3-28 years at last follow-up. A total of 28 events of corneal rupture were noted in 17 patients (eight male), among whom nine had had bilateral ruptures, and eight had had unilateral ruptures (four of the right cornea), while two had experienced re-rupture 2 and 4 years, respectively, after surgery; six patients (aged 3-21 years) had had no ruptures. We describe the natural history of our cases and discuss them together with those others reported in the literature. Because of similarities between the BCS and the kyphoscoliotic type of the Ehlers-Danlos syndrome (EDS VI), both disorders tend to have been confounded. Here, we show that all of our BCS patients tested in this regard had biochemical findings reflective of normal activity of lysyl hydroxylase, characteristically deficient in EDS VI, such as normal urinary total pyridinoline ratios and/or normal electrophoretic migration of collagen chains produced by dermal fibroblasts. The BCS is, therefore, an entity distinct from the kyphoscoliotic type of EDS, which has a much poorer prognosis.

Objective The authors reviewed the clinical features, diagnostic workup, and management of patients of penetrating orbital injuries with retained organic foreign bodies. Design Retrospective, noncomparative case series. Participants Nineteen patients (15 males, 4 females) with penetrating orbital injuries due to organic foreign bodies. Results The series included 15 (78.9%) males and 4 (21.1%) females who ranged in age from 6 months to 40 years (mean = 14.6 years); 12 (63.2%) patients were younger than 12 years of age. Twelve (63.2%) right and 7 (36.8%) left orbits were involved. Time between injury and presentation varied from a few hours to 9 months. Most common injury site was the superior orbit in 11 (57.9%) patients leading to abnormal extraocular motility (84.2%), proptosis (68.4%), and upper lid ptosis (47.4%). Associated pathologies also included acute cellulitis in 11, orbitocutaneous fistula in 5, and osteomyelitis in 2 patients. Preoperative computed tomography (CT) and magnetic resonance imaging (MRI) identified the foreign bodies in 42% and 57% of the patients, respectively. Conclusion Preoperative identification of the foreign material in the orbit was found to be very helpful for patient management but was only possible in approximately 50% of our cases with the use of CT and MRI. The vision in our patients usually improved shortly after treatment; the long-term complications more often included extraocular muscle and eyelid motility problems and periorbital scarring.

When basal cell carcinoma develops cystic change, its clinical and radiological features vary, leading to confusion in differential diagnosis. We report four cases with cystic formation of 62 patients with orbital and adnexal basal cell carcinoma encountered during the last 12 years. The salient clinical, radiological, and histopathological features of these cases are presented and differential diagnosis of large cystic lesions in the orbit is discussed. When the basal cell carcinoma develops cystic changes it mimics other orbital cysts, including inclusion cysts due to penetrating injury, mucoceles, and necrotic metastatic tumors.

Liposarcoma is a malignant tumor of adipose tissue. Considered the most common soft tissue sarcoma in adults, orbital liposarcoma is extremely rare. Most cases of orbital liposarcoma are primary and rarely metastatic. We report two cases of primary orbital liposarcoma with clinical presentation, radiologic studies (available for one case), and detailed histopathologic features. A brief review of primary orbital liposarcoma is also presented.