Search

Ghaida Alahmadi,1 Azza MY Maktabi,2 Gorka Sesma,1 Saleh Almesfer1 1Pediatric Ophthalmology and Strabismus Division, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia; 2Pathology and Laboratory Medicine Department, King Khaled Eye Specialist Hospital, Riyadh, Saudi ArabiaCorrespondence: Gorka Sesma, Pediatric Ophthalmology and Strabismus Division, King Khaled Eye Specialist Hospital, Al Urubah Branche Road, West Building 2 nd Floor, Riyadh, 11462, Saudi Arabia, Tel +966114849700, Fax +966114821908, Email gsesma@kkesh.med.saPurpose: To evaluate the efficacy of intravitreal chemotherapy for vitreous seeding in patients with retinoblastoma (Rb).Design: Retrospective, single-arm cohort study.Methods: This study was conducted at a tertiary eye center. Between 2013 and 2021, 27 patients (27 eyes) with vitreous Rb receiving adjuvant intravitreal melphalan (IVM) as secondary/salvage treatment in one eye were included. Patients who were unable to follow-up or treated elsewhere were excluded. Survival analysis was performed to assess the incidence of enucleation in the melphalan-treated group, as well as in bilateral cases with eyes receiving melphalan and those receiving standard treatment, consisting of chemotherapy, thermotherapy, and enucleation according to the disease stage.Results: The median (interquartile range) follow-up time was 65 months (range, 34– 83 months). Seventeen patients (63%) had bilateral disease. Sixteen eyes (59%) were saved. The Kaplan–Meier survival estimates for eyes receiving melphalan were 100% at 1 year (95% confidence interval [CI]:11.2– 14.3), 75% (95% CI:14.2– 48.9) at 3 years, and 50% at 5 years. Melphalan-treated patients with bilateral disease showed a significantly higher number of saved eyes than the standard treatment group (P=0.002). Tumor recurrence was the primary cause of enucleation, accounting for 36% of the cases. In the vitreous hemorrhage group, the odds of enucleation were 13 times higher (95% CI:1.04– 165.28) than in the group without this condition.Conclusion: IVM is an effective treatment option for vitreous seeds. After 3 years of follow-up, the estimated survival rate for saved eyes decreased, and vitreous hemorrhage significantly increased the likelihood of enucleation. Further studies are required to determine the precise effects of IVM.Graphical Abstract: Keywords: retinoblastoma, melphalan, intravitreal chemotherapy, ocular oncology, intraocular tumors

Introduction: Retinoblastoma is a serious childhood intraocular neoplasm that can be diagnosed clinically with the aid of B-scan ultrasound, and radiological examination. On the other hand, the differential diagnosis includes benign and other masquerading conditions such as uveitis and endophthalmitis thus adding challenge to the proper diagnosis., Presentation of Case: A six-year-old girl presented with leukocoria and decreased vision of the right eye. Patient was diagnosed and treated as a case of endophthalmitis elsewherewith no improvement. She was re-evaluated in our hospital and found to have cataract with ruptured capsule, and no view to the fundus. B scan was conducted and showed posterior cavity mass with calcification, and retinal detachment. Retinoblastoma was suspected and proved by examination under anesthesia. Enucleation was carried out and the diagnosis was further confirmed by histopathological examination., Discussion: Diagnosis of retinoblastoma can be challenging since leukocoria is the most common presenting complaint, which can be also seen in other benign conditions such as Coat's disease. It may also masquerade as endophthalmitis, uveitis with or without glaucoma, and retinal detachment. High suspicious of retinoblastoma in children and appropriate examination and work up with the aid of Biomicroscopy and radiological examination will help reaching the appropriate diagnosis saving patients unnecessary interventions with related morbidity., Conclusion: Retinoblastoma has a wide spectrum of clinical presentations and must be ruled out before performing any intraocular procedure., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The "C group" of the histiocytic disorders is characterized by non-Langerhans-cell histiocytic lesions in the skin, mucosal surfaces, or both, out of which Juvenile xanthogranuloma (JXG) is the most common typically affecting the skin. The eye is the most common extra-cutaneous site of JXG., we aim at providing our clinical and histopathological experience with this group of diseases including the adult-onset xanthogranuloma (AXG)., Methods: This is a retrospective cohort study of all patients with the tissue diagnosis of ocular and periocular cutaneous and mucocutaneous non-LCH disorders who presented to us over a period of 25 years (January 1993 to December 2018)., Results: Twenty patients were diagnosed as "Group C" disease with an age range of 2 months-60.9 years. Eleven patients were females (55%) and nine were males (45%). The involvement was mostly unilateral in 80.9%. All cases fell into the xanthogranuloma family with 11 JXG patients, 8 AXG patients of skin and ocular surface, and one patient with solitary reticulohistiocytoma (SRH). The clinical site of involvement in JXG was primarily in the eyelid in 5 patients (45%), ocular surface lesions in 2 (18%), iris in 2 (18%), choroidal and bilateral orbital lesions in 1 patient each (9%). The group of AXG, presented equally with eyelid lesions in 4/8 and ocular surface lesions in 4/8. The non-Langerhans' histiocytic infiltrate showed supportive immunohistochemical staining properties (reactive to CD68 marker and negative to S-100 and langerin markers)., Conclusion: Among the rare histiocytic disorders, xanthogranulomatosis is the commonest and has wide clinical manifestations. Accurate diagnosis needs to be supported by typical histopathological findings. JXG was the commonest in our study with relatively older mean age at presentation and frequent eyelid rather than iris involvement. AXG is often confused with xanthelasma when involving the eyelids with corneal limbal involvement is relatively frequent., (© 2024. The Author(s).)

Introduction and Importance: Medulloepithelioma is the second most common primary intraocular malignant tumor in children but is often diagnosed late, which worsens the prognosis., Case Presentation: We are reporting a 6-year-old boy presenting with a ciliary body (CB) teratoid malignant medulloepithelioma (TMM), which was missed at the initial presentation. We added our case to the 97 previously reported cases in our literature review that were confirmed by cytological or histopathological examination., Discussion: Medulloepithelioma has a wide age range at presentation with a mean of 5.3 ± 4.1 years, and slight male predominance (M: F ratio of 1.15). Clinically, the main symptoms/ signs are reduced visual acuity, lens changes, or a pupil "mass." Almost all reported medulloepitheliomas were unilateral (98 %). Histopathologically, non-teratoid malignant medulloepithelioma (NTMM) (35.7 %) and TMM (34.5 %) were the commonest. Enucleation was the main treatment modality because of the large tumor size of 72.7 %. A combination of chemotherapy and/or radiotherapy was used in 15.1 % and brachytherapy for small lesions in 14.1 %. Orbital exenteration was needed in 3 cases because of orbital invasion., Conclusion: A CB medulloepithelioma tumor can be easily missed, diagnosed late, with less chance for globe salvaging. The malignant types are more common and may result in orbital invasion, requiring even more extensive surgery. Therefore, when facing a child with lens changes, a pupil "mass," or raised intraocular pressure, pediatricians and general ophthalmologists must have an earlier suspicion and be aware of this rare entity to improve outcomes and reduce loss of vision or other disease-related morbidity., Competing Interests: Conflict of interest statement None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To report clinical features and treatment outcome of three cases with isolated corneal intraepithelial neoplasia (CIN)., Methods: This case series presents 3 patients with isolated CIN. Data collected included, presenting signs and symptoms including vision, anterior segment examination, medical and surgical outcomes and signs and symptoms at lost post-treatment visit., Results: Case 1 was a 45-year-old male who presented with an isolated grayish amoeboid corneal lesion which was excised with alcohol assisted epitheliectomy, he also received 6 cycles of topical mitomycin C (MMC) 0.02% and one injection of interferon alfa-2b with no recurrence during the 10-year follow-up period. Case 2 was 78-year-old male referred for a suspicious white corneal lesion which was completely excised, the patient also received 6 subconjunctival injections of interferon alpha-2b. However, the lesion recurred at 2.5-years post-treatment. Case 3 was a 63-year-old male patient who presented with an isolated corneal lesion that was excised using alcohol-assisted epitheliectomy, patient received four cycles of topical 5-fluorouracil with no recurrence at last follow-up visit at 6 months., Conclusion: Isolated corneal intraepithelial neoplasia (CIN) is a rare entity with few reported cases in the literature. In this case series, we report long and short-term management outcomes of combined surgical and medical therapy for isolated CIN., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Al-Swailem, Alkatan, AlDhaheri, AlHilali and Maktabi.)

Introduction: Apocrine cystadenomas are rare, benign tumors that might arise in the periocular region from glands of Moll. They characteristically demonstrate proliferative features on histopathological examination, which differentiate them from simple hidrocystomas., Presentation of Cases: We retrospectively identified 4 consecutive cases of apocrine cystadenomas in male patients with a mean age of 48.5 years (range 20-62). One of the cases was a recurrent lesion. The Preoperative clinical diagnosis was mostly hidrocystoma. All patients agreed on complete surgical excision of their cystic lesions. Histopathological review of the excised cysts confirmed the diagnosis of apocrine cystadenoma based on the presence of proliferative features with no atypia or infiltrative behavior. Cases are summarized in Table 1 and the histopathological appearance is demonstrated in the included figure., Discussion: Apocrine cystadenoma is rare. It occurs in the areas of skin with hair follicles, such as the axilla, neck, and trunk, and may be mistaken for other skin lesions, such as nevi or syringomas. In the eyelid region, they are commonly missed and frequently diagnosed as simple hidrocystoma due to the presence of bluish hue such as in our series. Recurrence is rare but was found in one of our patients at initial presentation. Our series included unique locations of this lesion in the medial canthus in one patient and near the eyelid tarsus in another., Conclusion: Ophthalmologist should be aware of the rare occurrence of this lesion in the periocular region. Further studies to explain the etiology of such proliferative nature in apocrine cysts would be interesting., Competing Interests: Conflict of interest statement Authors have no conflicts of interest in relation to this work., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Temporal artery (TA) biopsy is commonly used for the diagnosis of giant cell arteritis (GCA). However, a positive biopsy is no longer mandatory for diagnosis. This study aims to correlate the histopathological findings of TA biopsies in suspected cases of GCA to the clinical presentation in an ophthalmic tertiary eye care center to draw useful conclusions and advocate the possible implementation of guidelines for TA biopsy., Methods: Data was collected from patients' medical records including, demographics, clinical data, and histopathological findings and diagnosis. The 2022 American College of Rheumatology/ European Alliance of Associations for Rheumatology (ACR/EULAR) criteria have been used and partially adopted as a guide to compare the variables between TA biopsy-positive and negative groups as well as the TA biopsy-positive group and the group of patients with TA biopsy showing atherosclerosis., Results: Out of the total 35 patients who underwent a TA biopsy during the period of 23 years, 22.9% of patients had histopathological findings consistent with GCA and 42.9% had TA atherosclerotic changes, while the remaining 34.3% had histologically unremarkable TA. The mean age of all patients was 66 ± 10.9 years. Slightly more than half were females (54.3%) and the remaining were males (45.7%). In the group with positive TA biopsies, the mean age was 71 ± 8.4 years with a higher female predominance (female-to-male ratio of 5:3). The mean diagnostic clinical score used in our study was higher (7.5 ± 2.33) in the GCA-positive group when compared to the other groups with statistical significance (mean of 4.85 ± 2.01 in patients with overall GCA-negative biopsies and 5.13 ± 2.10 in the group with atherosclerosis). Other three clinical variables that were found to be statistically significant in the GCA biopsy-positive group were scalp tenderness, jaw claudication, and optic nerve pallor., Discussion: The mean age (71 ± 8.4 years) and the female predominance of GCA in our group of patients with positive TA biopsy (62.5%) was like other reports. In our study 22.9% of performed TA biopsies over the period of the study were positive confirming the diagnosis of GCA on histological exam, which was similar to another report and is considered to be relatively low. The incorporation of increased clinically focused assessments and algorithms, with the aid of the ACR/EULAR criteria, may decrease the frequency of TA biopsies that carries unnecessary cost and risk of procedure-related morbidity. We highly recommend applying the age of ≥ 50 years as an initial criterion for diagnosis, followed by the consideration of the statistically significant clinical features: scalp tenderness, jaw claudication, and optic nerve pallor., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Alkatan, AlMana and Maktabi.)

Purpose: The purpose of this study was to report the outcomes of using gamma-irradiated sterile cornea (GISC) as a deep lamellar keratoplasty (DALK) graft in a patient with keratoconus., Methods: This is a case report., Results: A 33-year-old male patient diagnosed with keratoconus underwent DALK using a GISC and developed a persistent epithelial defect which eventually led to sterile keratolysis necessitating further surgical interventions. Management and slitlamp photography, anterior segment optical coherence tomography (AS-OCT), and histopathological examination of the explanted graft are described in detail., Conclusions: This is the first reported case of sterile keratolysis after the use of GISC lenticule in DALK in a healthy patient with keratoconus. The underlying pathophysiology is not clearly understood, and some theories have been proposed in this report. Surgeons need to be aware of this rare complication and are encouraged to have a low threshold for graft replacement to ensure good clinical and visual outcomes. Developing a prospective complication registry to document complications after the use of GISC lenticules in ophthalmic surgery is recommended., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Orbital inflammatory disease (OID) encompasses a wide range of pathology including thyroid-associated orbitopathy (TAO), granulomatosis with polyangiitis (GPA), sarcoidosis and non-specific orbital inflammation (NSOI), accounting for up to 6% of orbital diseases. Understanding the underlying pathophysiology of OID can improve diagnosis and help target therapy., Aims: To test the hypothesis that shared signalling pathways are activated in different forms of OID., Methods: In this secondary analysis, pathway analysis was performed on the previously reported differentially expressed genes from orbital adipose tissue using patients with OID and healthy controls who were characterised by microarray. For the original publications, tissue specimens were collected from oculoplastic surgeons at 10 international centres representing four countries (USA, Canada, Australia and Saudi Arabia). Diagnoses were independently confirmed by two masked ocular pathologists (DJW, HEG). Gene expression profiling analysis was performed at the Oregon Health & Science University. Eighty-three participants were included: 25 with TAO, 6 with orbital GPA, 7 with orbital sarcoidosis, 25 with NSOI and 20 healthy controls., Results: Among the 83 subjects (mean (SD) age, 52.8 (18.3) years; 70% (n=58) female), those with OID demonstrated perturbation of the downstream gene expressions of the IGF-1R (MAPK/RAS/RAF/MEK/ERK and PI3K/Akt/mTOR pathways), peroxisome proliferator-activated receptor-γ (PPARγ), adipocytokine and AMPK signalling pathways compared with healthy controls. Specifically, GPA samples differed from controls in gene expression within the insulin-like growth factor-1 receptor (IGF-1R, PI3K-Akt (p=0.001), RAS (p=0.005)), PPARγ (p=0.002), adipocytokine (p=0.004) or AMPK (p=<0.001) pathways. TAO, sarcoidosis and NSOI samples were also found to have statistically significant differential gene expression in these pathways., Conclusions: Although OID includes a heterogenous group of pathologies, TAO, GPA, sarcoidosis and NSOI share enrichment of common gene signalling pathways, namely IGF-1R, PPARγ, adipocytokine and AMPK. Pathway analyses of gene expression suggest that other forms of orbital inflammation in addition to TAO may benefit from blockade of IGF-1R signalling pathways., Competing Interests: Competing interests: JTR has in the past consulted for Genentech/Roche and was a coinvestigator on a study funded by Genentech to evaluate the use of rituximab for orbital inflammatory diseases. JTR, RAD, BSK, DOK, and GJH are consultants to Horizon Pharmaceuticals which manufactures teprotumumab. JTR receives research support from Horizon Pharmaceuticals., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To determine the incidence of cosmetic-related lacrimal sac black deposits (LSBDs) in primary-acquired nasolacrimal duct obstruction (PANDO) biopsies and the role of LSBD in the pathogenesis of PANDO, in addition to their association with dry eye disease (DED)., Methods: A clinicopathological study included all patients who underwent surgical management of PANDO. We excluded patients in whom lacrimal sac biopsy was not taken during the surgery. Lacrimal sac tissues were evaluated for the presence of LSBD and related inflammation, with correlation to the demographics, clinical presentation, and pre-operative clinical assessment of dry eye. P <0.05 was considered statistically significant., Results: Of the 177 PANDO specimens, black deposit aggregates were noted in the sac stroma of 61 lacrimal sac specimens (34.5%; 95% confidence interval: 27.5-47.5). LSBDs were significantly more common in females ( P < 0.001). The age, residence, past ailments, and laterality were not associated with LSBD. Dry eye was more common with LSBD ( P = 0.004). Other presenting symptoms were not significantly associated with LSBD. The stromal black deposits in biopsies were mostly extracellular or in macrophages. The LSBD in only 10 specimens demonstrated birefringence. Energy dispersive spectroscopy determined that carbon and sulfur were the main elements in the black aggregates., Conclusion: Cosmetic-related LSBD is unlikely to play a role in the pathogenesis of PANDO. However, they were significantly associated with DED., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Saudi Journal of Ophthalmology.)

Purpose: Nasopharyngeal carcinoma (NPC) is an aggressive malignant tumor that arises from the nasopharyngeal epithelial lining. Most patients with NPC present with a neck mass or cranial nerve palsy. It is infrequent for patients with NPC to present to an ophthalmologist initially with ophthalmic complaints and absence of prior diagnosis of NPC. We are reporting a series of six NPC cases that presented solely with ophthalmic complaints, to attract the attention of ophthalmologist to such a serious neoplasm., Methods: A retrospective observational study of all consecutive patients diagnosed with NPC based on their initial ophthalmic presentation with no prior diagnosis of this neoplasm. Patients presented for the first time to two tertiary eye hospitals. Data were collected by the chart review for demographics, clinical presentation, radiological imaging, treatment regimen, and follow-up. Histopathological review of their tissue specimens was conducted by two pathologists., Results: We had six patients who presented for the first time to our ophthalmic service complaining mostly of limitation of extraocular muscle motility with or without diplopia (4/6), orbital or facial pain (2/6), and disturbance in vision (2/6). The age ranged from 35 to 92 years with a mean of 58 years. A male predominance was observed with male-to-female ratio of 5:1. The cases are described along with their imaging and histopathological findings. Relevant literature review was also presented. Most of our patients (5/6) received combination of radiotherapy and chemotherapy. One patient refused treatment and 2 eventually passed away after 7 months., Conclusion: Ophthalmologists may play a major role in diagnosing such patients accurately and referring them for early management and better prognosis., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Saudi Journal of Ophthalmology.)

Purpose: Ophthalmic histiocytic lesions comprise a heterogeneous rare group of disorders that are characterized by an abnormal proliferation of histiocytes and may affect all age groups of both sexes. The aim of this study was to highlight the basic demographic, clinical, and histopathological characteristics of this rare group of diseases in ophthalmic practice, which has not been previously studied in this area. Only individual cases have been previously reported., Methods: This was a retrospective study of all biopsied ocular and periocular histiocytic lesions from two centers, King Khaled Eye Specialist Hospital (KKESH) and King Abdulaziz University Hospital (KAUH) in Riyadh, Saudi Arabia, from January 1993 to December 2018. The histopathological diagnosis was confirmed, and the cases were re-classified by reviewing all histopathological slides. The corresponding demographic and clinical data were analyzed. A relevant literature review was also carried out for comparison of our collected analyzed data to published data and to draw our own conclusions., Results: A total of 34 ocular/periocular histiocytic lesions in 28 patients who were mostly Saudis (92.9%) were included. The male-to-female ratio was 4:3. The median age at presentation was 6.4 years (range: 2.8-35 years). Twenty-two patients had unilateral involvement, and six patients had bilateral lesions. In patients with Langerhans cell histiocytosis (LCH; L group), the most common presenting findings were eyelid swelling (75%), periocular tenderness (37.5%), proptosis/globe displacement (37.5%) eyelid erythema (25%), and orbital pain (12.5%). In patients with Rosai Dorfman disease (RDD; R group), proptosis/globe displacement occurred in all patients and 80% had decreased vision. Patients in the C group (Cutaneous non-LCH histiocytoses) had variable clinical features because of the different locations of the histiocytic lesions, with the majority involving the eyelids (66.7%). Diagnosis was accurately reached clinically in 38.8%, 33.7%, and 46.7% of patients in the L, C, and R groups, respectively. Overall, the clinical diagnosis was in concordance with the histopathologic diagnosis in 14 out of 34 lesions (41.2%)., Conclusions: Histiocytic disease is more likely to be overlooked clinically owing to its rarity. In the C group, juvenile xanthogranuloma (JXG) was the most commonly encountered histiocytic lesion and had a tendency to present at a later age with extremely rare intraocular involvement in contrast to previously published reports. The median age at presentation was higher in group R. All patients in group L had strictly unilateral disease, while RDD (group R) was most commonly bilateral. Future research on genetic aspects, management, and prognosis is necessary., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Microphthalmia is a rare ocular anomaly with a poorly understood etiology that is most likely related to heritable and/or environmental factors. Many papers have been published pertaining to the clinical manifestations and management of this condition; however, few reports have reported detailed histopathological findings, which are the focus of this study, in addition to highlighting the basic demographics in these cases. This was a retrospective, observational study of all consecutive enucleated microphthalmic globes (with or without cysts) at 2 tertiary eye hospitals in Riyadh, Saudi Arabia. Globes were classified into 2 groups: severe microphthalmos (axial length or mean diameter less than 10 mm in infancy or 12 mm after age 1 year) and mild microphthalmos based on larger measurements. Clinical and demographic data collected included sex, age at enucleation, eye involvement, nationality/region, consanguinity, family history of eye anomaly, pregnancy, systemic disease, or syndromes. For histopathological data, a descriptive analysis was mostly performed. For correlations of some of our qualitative data, Fisher's exact test was used. Eleven cases (6 mild and 5 severe microphthalmos) were initially identified with a female to male ratio of 4:7. Ten patients were Saudis, 7 of whom were from the central region. Consanguinity was found in 36% (4/11), and 3 of them had other ocular or systemic abnormalities (duodenal atresia, microcephaly, kidney agenesis, cryptophthalmos, and dysmorphic facial features). Histopathological data were available for 10 cases, half of which showed a coloboma and/or anterior segment anomaly. There was no significant correlation among gender, severity of microphthalmos or the presence of coloboma, although severe microphthalmic globes had a higher median of abnormal intraocular structures (9-interquartile range = 2 compared to 6-interquartile range = 1 in the mild group). Aphakia was found in half of the globes with associated anterior segment dysgenesis. We have concluded that microphthalmos is a visually disabling congenital anomaly that can be isolated or associated with other periocular or systemic anomalies, possibly in relation to consanguinity in our cases. Congenital aphakia was found in half of these cases and was mostly associated with absent Descemet's membrane and agenesis of anterior chamber angle structures, supporting previously suggested embryological concepts. These findings necessitate further wider genetic testing and proper premarital counseling in Saudi Arabia., (© 2022. The Author(s).)

Introduction: Sturge-weber syndrome (SWS) is a rare condition that presents with a typical facial port-wine stain, neurological manifestations such as seizures, and ocular involvement by glaucoma and/or choroidal hemangioma. In this series we demonstrate the histopathological details of the primary ocular involvement as well as the late blinding secondary ocular changes., Presentation of Cases: Seven cases were included with the diagnosis of choroidal hemangioma in association with SWS (6 enucleations and one evisceration). Male to female ratio was 4:3. Age at enucleation/evisceration ranged from 25 to 68 years with a median of 42 years. Five cases had history of glaucoma (71.4%). Diffuse hemangioma was found in all (4 cavernous and 3 mixed cavernous/capillary type). Conjunctival and episcleral hemangiomas were found in 3/7. Iris neovascularization and retinal detachment were confirmed in 5/7 cases each (71%)., Discussion: Our demographic and histopathological findings parallel what was previously concluded in the literature about the lack of gender predilection in SWS, and the most common ocular presentations of glaucoma and choroidal hemangioma, which is mostly diffuse in nature. The hemangioma type was found to be mostly cavernous followed by mixed capillary and cavernous. We demonstrated late associated ocular changes such as cataract, iris neovascularization, exudative retinal detachment, retinal pigment epithelium hyperplasia/metaplasia, and optic nerve atrophy, all of which aid in the poor visual outcome in these patients., Conclusion: Sturge-weber syndrome is a rare but visually disabling disease due to the associated ocular manifestations of glaucoma and choroidal hemangioma. Multidisciplinary approach because of the diverse presentation of this condition by pediatrician, neurologist, and ophthalmologist is essential with an attempt to preserve vision., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: To provide basic demographic information and clinicopathologic features of ophthalmic Rosai-Dorfman disease (RDD) with a literature review., Methods: A multi-centre retrospective case series reviewing all patients with histopathologically confirmed ophthalmic RDD at three tertiary eye care centres between January 1993 and December 2018., Results: Eleven eyes of eight patients with histopathologically confirmed ophthalmic RDD were included, with equal numbers of males and females. The median age was 40.25 years (range: 26.6-72.4). Two patients had familial RDD. The orbit was the most commonly involved site (90.9% eyes). One patient (one eye) presented with a scleral nodule, anterior uveitis and cystoid macular oedema. Visual acuity ranged from 20/25 to light perception. Six patients had an extra-nodal ophthalmic disease, and the remaining two had an associated submandibular lymphadenopathy (nodal RDD)., Conclusions: Ophthalmic RDD can be the only manifestation of this systemic disease, with the orbit being the most commonly involved site, exhibiting bone destruction, intracranial and/or sinus involvement and variable degree of visual loss. Ophthalmic familial RDD represent a severe form with a malignant course. Steroid monotherapy may be inadequate to control orbital RDD; thus, combined treatment is usually necessary. A comprehensive approach to assessment and management is recommended., (© 2021. The Author(s).)

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<0.001 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., Competing Interests: The authors have declared that no competing interests exist.

BACKGROUND Melanocytoma is rare and can affect any part of the uveal tract. In rare cases, iris melanocytoma shows signs of growth, with extrascleral extension that mimics melanoma. This phenomenon makes clinical differentiation between the 2 pathologies particularly challenging. CASE REPORT A 3-year-old boy presented with recurrent ocular inflammation. Examination revealed a large, solid, homogenous mass in the inferior quadrants of the iris, with secondary localized corneal edema. The lesion did not extend to the ciliary body and fundus examination showed no lesions in the posterior segment, including the head of the optic nerve. The patient underwent a sectoral iridocyclectomy and excisional biopsy of the lesion in the iris. Histopathology of the lesion confirmed the diagnosis of iris melanocytoma. CONCLUSIONS The differential diagnosis for a mass in the iris is broad, ranging from benign cysts to melanoma, which is a life-threatening ocular condition. An iris melanocytoma always should be considered in the differential of these masses, despite their exceedingly low incidence. Although iris melanocytoma mainly manifests in patients who are middle-aged or older, it should be suspected in young children, as underscored by the present report.

Several methods have been implemented to obtain suitable samples from patients for the purpose of histopathological examination and definitive diagnosis. This has been of paramount importance in dealing with oncology cases including orbital neoplasms. Open surgical biopsy has been the common standard technique used in our eye centers in Saudi Arabia for diagnosing various orbital lesions. Other modalities such as fine-needle aspiration biopsy, core biopsy, and imaging-guided core biopsy are not popular. We report two cases where open surgical biopsies may have not been optimal in reaching the desired tissue diagnosis of orbital malignancy on time, thus resulting in delaying further management of the two patients., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Saudi Journal of Ophthalmology.)

Introduction and Importance: Juxtapapillary retinal capillary hemangiomas (RCHs) are vascular hamartomas that occur adjacent to the optic disc. Juxtapapillary RCHs can be found as an isolated finding or in association with Von Hippel-Lindau (VHL) disease. VHL is a dominantly inherited disease that is characterized by multiple intracranial and retinal hemangioblastomas along with benign and malignant visceral tumors. RCH is a hallmark lesion in VHL and typically presents early in the disease., Case Presentation: We present the clinical and histopathological findings of a 15-month-old child with juxtapapillary RCH associated with exudative retinal detachment and a family history of VHL. The child presented initially at a late stage and lost to follow-up twice then came back with a blind painful eye secondary to neovascular glaucoma necessitating enucleation., Discussion: Although juxtapapillary RCHs are benign, slowly growing tumors, they pose a serious threat to central vision secondary to posterior segment complications such as intraretinal and subretinal exudation, macular edema and exudative retinal detachment and anterior segment complications such neovascular glaucoma if left untreated., Conclusion: Juxtapapillary RCHs are potentially blinding tumors if not treated in early stages given their close proximity to the optic nerve (ON) and macula., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: The management of bilateral advanced retinoblastoma (RB) cases is challenging with attempts to use neoadjuvant therapy salvaging of one of the globes. Our aim in this study was to demonstrate the effect of this primary therapy on the histopathological features and risk factors in secondary enucleated compared to primarily enucleated globes with groups D and E RB., Methods: We retrospectively reviewed all enucleated globes with advanced RB received in the pathology laboratories over a period of 5 years. Patients were divided into two groups: one with primary enucleations and another with at least one secondary enucleated globe, and their demographic and clinical data were analyzed. The enucleated globes in the two groups were analyzed to compare the general histopathological features including tumor seeding, size, differentiation, growth pattern, mitotic figures, and focality. More importantly, high-risk features: choroidal invasion, optic nerve (ON) invasion, iris/anterior chamber invasion, ciliary body invasion, and scleral and extra-scleral extension, as well as the pathological classification of the tumor (pT) according to the American Joint Committee on Cancer 7th edition were also compared between the two groups., Results: We had a total of 106 enucleated globes (78 primary and 28 secondary enucleations) from 99 patients with advanced RB (73 patients with primarily and 26 with secondarily enucleated globes). Demographic and clinical profiles of patients were similar in both, but the mean interval from presentation to enucleation was significantly longer in the secondary enucleations (P = 0.015). Rare/occasional mitotic figures were observed in secondary enucleations using multivariate analysis (P = 0.003). Primarily enucleated globes had higher risk of tumor seeding (P = 0.020), post-laminar/surgical margin ON invasion (P = 0.001), and massive choroidal invasion (P = 0.028). Half of the secondary enucleated globes had tumors confined to the globes without invasion (pT1) and statistically significant lower tumor classifications (pT1 or pT2a) compared to primary enucleations (P =0.001). However, 18% of the secondarily enucleated globes in 3 patients had unfavorable outcome with RB-related mortality after a period of 1-4 years., Conclusions: Secondary enucleated globes with advanced RB show favorable histopathological findings mainly less mitosis. These eyes have significantly lower chance for harboring choroidal and ON invasion, thus mostly classified as pT1 or pT2a when compared to primarily enucleated globes. The decision for secondary enucleation was observed to be significantly delayed (8.0 months ± 9.8). Prompt decision for needed enucleation based on the response to primary treatment and careful histopathological examination of enucleated globes are essential to prevent disease-related mortality.

Background: Whipple's disease (WD) is a rare, chronic, infection caused by gram-positive filamentous aerobic actinobacterium Tropheryma whipplei occurs classically in the gastrointestinal tract and shows histopathologically foamy macrophages with typical numerous PAS-positive, non-acid fast particles. Ocular WD in the form of uveitis may occur in the absence of systemic disease but has not been reported to present with scleral manifestation. We describe for the first time to the best of our knowledge 2 cases of scleral nodules with typical histopathological morphology of WD and without systemic involvement., Case Presentation: The first was a 53-year old diabetic male farmer who presented with 2 nontender right eye scleral nodules for 3 months, had a negative systemic workup, and surgical excision showed Periodic acid Schiff (PAS)-positive eosinophilic structures inside macrophages. Grocott's methenamine silver (GMS) stain and acid-fast bacilli (AFB) stain of the tissue itself were negative. The second case was a 60-year old male who presented with an asymptomatic superior scleral nodule for 4 months, which showed similar appearance and negative GMS and AFB stains., Conclusion: WD should be included in the differential diagnosis of scleral nodules even in the absence of systemic symptoms. Surgical excision without systemic treatment resulted in successful outcome without recurrence.

Background: Optic nerve (ON) invasion is an important high-risk feature, and an indicator for neoadjuvant chemotherapy and prognosis. We aim through this study to correlate the detected-ON invasion by Magnetic resonance imaging (MRI) with the corresponding confirmed histopathological level of invasion., Methods: A retrospective study of enucleated globes with the diagnosis of retinoblastoma received in the histopathology department(s) from January 2015 to December 2016 (2 years). Slides were reviewed for ON invasion assessment, charts were reviewed for basic demographic data. All patients underwent MRI under sedation upon diagnosis and MRI findings were collected for the above correlation., Results: A total of 38 patients were included: 21 males and 17 females. 29 (77.3%) had unilateral involvement, 7 (18.4%) had bilateral involvement and 2 cases had trilateral disease. The overall mean age at diagnosis was 22.63 ± 15.15 months. Histopathological examination revealed ON invasion in 28 cases (74%) distributed as follows: prelaminar (31.6%), laminar (18.4%), and post-laminar (23.7%). MRI confirmed post-laminar ON invasion in 8 cases (true positive) but failed to detect this in 1 case. Additionally, MRI detected another 8 cases of ON invasion that were false positive on histopathology (accuracy: 63.3%; sensitivity: 88.9%; specificity: 72.4%; Positive predictive value (PPV): 50%; Negative predictive value (NPV): 95.5%)., Conclusions: MRI is found to be less sensitive in evaluating prelaminar and laminar ON invasion (0.0 and 42.9%) compared to post-laminar invasion (88.9%). MRI has generally better specificity in detecting ON invasion irrespective of the invasion level. In our study, obtaining deeper and/or additional histologic sections from the other surface of the tissue block in cases where a post-laminar ON invasion by MRI is found but not confirmed histopathologically in routine sections is essential to avoid missing such an important high-risk feature.

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., Competing Interests: The authors have no financial or conflict of interest related to this work., (Copyright © 2019 by S. Karger AG, Basel.)

Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder that has been found in all continents and racial groups in relation to faulty repair of DNA with sun exposure. Several cutaneous and ocular tumors have been described in relation to XP including fibrous histiocytoma (FH). The diagnosis of conjunctival FH is challenging owing to the rarity of this tumor and the diversity of its classification into benign, locally aggressive and malignant. We are describing a recurrent FH exhibiting a locally aggressive behavior in a child with history of XP. Detailed histopathological features are presented with literature review., (© 2017 The Authors.)

Objective: Orbital Rhabdomyosarcoma is a highly malignant tumor predominantly affecting children. Our study adds more understanding of this tumor to ophthalmologists from the clinicopathological, radiological and genetic aspects., Design: A retrospective clinicopathological and radiological study of ocular rhabdomyosarcoma with genetic profiling., Participants: All the cases with confirmed tissue diagnosis of orbital rhabdomyosarcoma presenting at a tertiary eye hospital in Riyadh, Saudi Arabia during the period 1985-2015., Methods: Charts and histological slides of 26 patients were reviewed. DNA was extracted from paraffin-embedded biopsies and genotyping was performed to detect chromosomal abnormalities and Copy-number variations regions., Results: 18 males and 8 females were included with a mean age at presentation of 6.9 years (SD of 4.4). Proptosis and globe displacement were the commonest clinical presentations. Embryonal histopathological type was the commonest (73.1%) with superior orbital involvement (p = 0.024). Using magnetic resonance imaging, the embryonal type showed higher Apparent diffusion coefficient (ADC) value compared to the alveolar type (p = 0.98). Genetic profiling showed Copy-number gain in regions spanning PAX3, DDIT3, Gli, Wnt6 genes. DICER1 gene implication was found in 9 sporadic cases., Conclusion: Rhabdomyosarcoma is rare and occurs with a mean age of 7 years, predominantly among males. The commonest embryonal type is significantly correlated with superior orbital involvement. Radiologically, it shows an ADC of 0.67-0.09 × 10 -3 mm 2 /s. (p = 0.98). The gain in PAX3, DDIT3, Gli1, Wnt6 genes is a new finding while the DICER1 gene implication in the absence of familial hereditary carcinoma is another interesting finding., (Copyright © 2019 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the importance of "en toto" globe submission in the assessment of high-risk pathological findings in retinoblastoma cases, aiming at identifying the additional value from full globe examination of enucleated eyes (including the calottes)., Methods: Retrospective histopathological case series of eighty-one enucleated globes with the clinical diagnosis of retinoblastoma, histopathologically examined at King Khaled Eye Specialist Hospital (KKESH) between January 2010 and December 2013. We included retinoblastoma eyes with any type of invasion (more than pT1) in which the globe was submitted "en toto." All cases were histopathologically classified according to the American Joint Cancer Classification (AJCC TNM classification, 2009 6th edition)., Results: 81 enucleated globes were examined, out of which 30 globes were classified as high-risk cases (more than pT1). 8 cases had massive choroidal invasion in both the PO sections and calottes. 5 cases had focal choroidal invasion in both. One case has massive choroidal invasion in calottes with very superficial ON head invasion. Two cases were found to have focal choroidal invasion in the calottes with prelaminar ON invasion. In these three cases (10%), the presence of focal or massive choroidal invasion in the calottes has affected the classification., Conclusions: This study consolidates the guidelines recommended in the consensus meeting: from the International Retinoblastoma Staging Working Group on the pathology guidelines for the examination and evaluation of prognostic risk factors in retinoblastoma eyes. Full globe submission and examination should be the routine accepted practice universally even in underdeveloped countries.

Background: Hematic cyst is a rare orbital condition that has a wide range of clinical presentation and is characterized pathologically by lack of endothelial lining., Purpose: To correlate clinical and radiological features of hematic cysts, to tissue diagnosis, and investigate the possible etiology behind this condition, its relation to trauma and other interesting histopathological findings., Methods: Retrospective case series at King Khaled Eye Specialist Hospital (KKESH) and King Abdulaziz University Hospital (KAUH) of all orbital lesions with tissue findings supporting the clinical and/or radiological diagnosis of hematic cyst., Results: A series of 13 cases was studied, 8 males and 5 females. Age ranged from 2 to 84 years with a median of 54. Most cases presented with proptosis (76.9%) and limitation of eye movements (69.2%). History of trauma was confirmed in only 2/13. The clinical diagnosis of hematic cyst was made prior to surgery in 38.4%. Magnetic Resonance Imaging (MRI) confirmed the presence of blood in the orbit in 7/7. Surgical intervention was the mainstay of treatment. Histopathologically, these lesions demonstrated variable constituents including blood break-down products (hemosiderin), macrophages, mononuclear inflammatory cells, hemorrhage, absent endothelial lining, reactive fibrosis and capsule-like formation. Cholesterol clefts with typical granulomas and multinucleated giant cells were present in 2 cases. A clue to an underlying vascular lesion was found histopathologically in 30.8%. None of the patients developed recurrence or long-term complications with an average follow up period of 1 year., Conclusion: Hematic cyst is a challenging clinical diagnosis that can be aided by radiological examination and histopathological confirmation. Trauma does not seem to play a major role while presence of a pre-existing vascular lesion with spontaneous hemorrhage may be an etiologic factor. Associated cholesterol granuloma is an interesting controversial finding. Surgical intervention is curative with possible persisting motility disturbance and/or the eye deviation and worse prognosis in post-traumatic cases.

Mesenchymal chondrosarcoma (MCS) is an unusual tumor mainly found in the skeleton. Around third of the cases occur in extra-skeletal sites with the orbit being the third most common site in these cases. In previous reviews of the orbital cases, it has been concluded that orbital MCS tends to occur in women in the second or third decades of life. However, 8 cases of orbital MCS have been reported so far in the pediatric age group (age less than 18 years-old) one of which has been considered congenital MCS in a 5-days old newborn girl. We describe 3 additional pediatric cases with primary orbital MCS and they were all males. Our cases presented with proptosis and calcific orbital masses on imaging studies. Histopathological examination of the excised masses shared the typical presence of undifferentiated mesenchymal cells and immature areas of cartilage. The diagnosis of MCS was further confirmed by immunohistochemical staining. Brief review of the literature in relation to this diagnosis in the orbit is also presented.

Importance: Although a variety of well-characterized diseases, such as sarcoidosis and granulomatosis with polyangiitis, affect the lacrimal gland, many patients with dacryoadenitis are diagnosed as having nonspecific orbital inflammation (NSOI) on the basis of histology and systemic disease evaluation. The ability to further classify the disease in these patients should facilitate selection of effective therapies., Objective: To test the a priori hypothesis that gene expression profiles would complement clinical and histopathologic evaluations in identifying well-characterized diseases and in subdividing NSOI into clinically relevant groups., Design, Setting, and Participants: In this cohort study, gene expression levels in biopsy specimens of inflamed and control lacrimal glands were measured with microarrays. Stained sections of the same biopsy specimens were used for evaluation of histopathology. Tissue samples of patients were obtained from oculoplastic surgeons at 7 international centers representing 4 countries (United States, Saudi Arabia, Canada, and Taiwan). Gene expression analysis was done at Oregon Health & Science University. Participants were 48 patients, including 3 with granulomatosis with polyangiitis, 28 with NSOI, 7 with sarcoidosis, 4 with thyroid eye disease, and 6 healthy controls. The study dates were March 2012 to April 2017., Main Outcomes and Measures: The primary outcome was subdivision of biopsy specimens based on gene expression of a published list of approximately 40 differentially expressed transcripts in blood, lacrimal gland, and orbital adipose tissue from patients with sarcoidosis. Stained sections were evaluated for inflammation (none, mild, moderate, or marked), granulomas, nodules, or fibrosis by 2 independent ocular pathologists masked to the clinical diagnosis., Results: Among 48 patients (mean [SD] age, 41.6 [19.0] years; 32 [67%] female), the mclust algorithm segregated the biopsy specimens into 4 subsets, with the differences illustrated by a heat map and multidimensional scaling plots. Most of the sarcoidosis biopsy specimens were in subset 1, which had the highest granuloma score. Three NSOI biopsy specimens in subset 1 had no apparent granulomas. Thirty-two percent (9 of 28) of the NSOI biopsy specimens could not be distinguished from biopsy specimens of healthy controls in subset 4, while other examples of NSOI tended to group with gene expression resembling granulomatosis with polyangiitis or thyroid eye disease. The 4 subsets could also be partially differentiated by their fibrosis, granulomas, and inflammation pathology scores but not their lymphoid nodule scores., Conclusions and Relevance: Gene expression profiling discloses clear heterogeneity among patients with lacrimal inflammatory disease. Comparison of the expression profiles suggests that a subset of patients with nonspecific dacryoadenitis might have a limited form of sarcoidosis, while other patients with NSOI cannot be distinguished from healthy controls.