Clinicopathological study of ophthalmic cutaneous and mucocutaneous non-langerhans cell histiocytic lesions.

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.

An advanced case of pediatric ciliary body medulloepithelioma with detailed literature review.

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.

Peri-ocular proliferative apocrine hidrocystoma (cystadenoma): A clinicopathological case series.

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.

Ocular Survival Following Intravitreal Melphalan as Adjuvant Treatment for Vitreous Retinoblastoma Seeding.

Purpose: 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.

Acute Sterile Keratolysis After Deep Anterior Lamellar Keratoplasty in a Patient With Keratoconus: A Case Report.

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.

Long-term outcomes and causes of intrastromal corneal ring segment explantation in a tertiary eye hospital.

PURPOSE: To evaluate the causes and long-term outcomes after intrastromal corneal ring segment (ICRS) explantation in the King Khaled Eye Specialist Hospital. METHODS: This was retrospective cohort study. Two groups were analyzed: Group one, ICRS surgery done in our hospital (n = 41) and group two, surgery done outside but removed in our hospital (n = 29). Causes and postoperative management after ICRS removal were analyzed. For statistical analysis, groups were analyzed into two subgroups of causes of ICRS removal: Visual disturbance versus extrusion/infection/neovascularization (NV) subgroups; and two subgroups of postoperative treatment: Corneal transplant (CT) versus Contact lens (CL)/eyeglasses subgroups. RESULTS: The most common cause of ICRS removal in group one was visual disturbance (45.2%) while in group two was extrusion (41.2%). CL is the preferable management after explantation. 76% of ICRS removal occurred during the first 4 years. In group 1, there was significant worse preimplantation visual acuity (P = 0.02) in CT subgroup versus CL/eyeglasses. CT subgroup had lower pachymetry of 437.4 µm (P = 0.04) and higher myopia of 8.05 (P = 0.03) than CL/eyeglasses subgroup. For group two, there was a significant improvement in uncorrected visual acuity in visual disturbances subgroup after explantation (P = 0.004). After explantation, visual disturbances subgroup had higher myopia -4.4 than extrusion subgroup -1.15 (P = 0.004). CONCLUSION: Seventy-six percent of ICRS removal occurred during the first 4 years. High myopia and pachymetry lower than 437 um were associated with visual disturbances and further management with corneal transplantation. High myopia was also associated with visual disturbances in surgeries done outside our hospital.

Demographics and histopathological characteristics of enucleated microphthalmic globes.

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.

Ophthalmic histiocytic lesions: a baseline demographic and clinicopathological study of 28 cases from two eye centers.

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.

Dacryops and clinical diagnostic challenges.

OBJECTIVE: The study aims to describe the clinical and histopathologic features of different types of dacryops and their clinical diagnostic challenges. METHODS: This is a retrospective cohort study of all surgically excised cases of dacryops in 2 tertiary eye hospitals in Riyadh, Saudi Arabia. RESULTS: The study included 58 dacryops specimens from 55 patients with an average age of 41.2 years (range, 4-78 years). The most common location was the upper lid (60.3%), whereas the least expected location was the caruncle (6.9%). The most common site of dacryops occurrence was in the accessory lacrimal gland (55.2%), the main lacrimal gland (32.8%), and then ectopic dacryops (12%). All patients presented with lid swelling alone except for 3 patients who experienced secondary mechanical ptosis. On physical examination, conjunctival scarring existed in 4 patients (6.9%). Preoperative diagnosis of dacryops was accurate in 44.8% of the cases. Dacryops of the main lacrimal gland was accurately diagnosed clinically in all cases compared with other locations, which was statistically significant (p < 0.001). The causes of inaccurate clinical diagnoses were hidrocystoma (26.9%), inclusion cyst (11.5%), and dermoid cyst (7.7%), whereas the remaining cases were diagnosed as cysts without a specific subtype (53.9%). Recurrence of the lesion was observed in 2 cases (3.5%). No clinical or histopathologic factors were associated with a risk of recurrence. CONCLUSION: Dacryops can represent a diagnostic challenge to ophthalmologists. Familiarity with clinical presentations and findings is required to diagnose dacryops outside the main lacrimal gland.

Enrichment of IGF-1R and PPARγ signalling pathways in orbital inflammatory diseases: steps toward understanding pathogenesis.

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.

Choroidal hemangioma in Sturge Weber syndrome: Case series with confirmed tissue diagnosis.

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.

Ophthalmic Rosai-Dorfman disease: a multi-centre comprehensive study.

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.

The clinico-pathologic profile of primary and recurrent orbital/periorbital plexiform neurofibromas (OPPN).

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.

Iris Melanocytoma in a Child: Clinical and Histopathological Findings.

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.

Juxtapapillary retinal capillary hemangioma: A clinical and histopathological case report.

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.

Nasopharyngeal carcinoma (NPC) in the ophthalmic practice: A serious neoplasm presenting initially to ophthalmologists.

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.

The association of cosmetic-related lacrimal sac black deposits with primary-acquired nasolacrimal duct obstruction and dry eye disease.

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.

Whipple's disease scleral nodules: a novel presentation in 2 consecutive patients.

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.

Histopathological assessment of optic nerve invasion guided by radiological findings in enucleated globes with retinoblastoma.

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.

High-risk features in primary versus secondary enucleated globes with advanced retinoblastoma: a retrospective histopathological study.

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.