Development of dual-functional core-shell electrospun mats with controlled release of anti-inflammatory and anti-bacterial agents for the treatment of corneal alkali burn injuries.

In this study, a novel dual-drug carrier for the co-administration of an anti-inflammatory and antibiotic agent consisting of core-shell nanofibers for the treatment of cornea alkali burns was designed. The core-shell nanofibers were prepared via coaxial electrospinning of curcumin-loaded silk fibroin as the core and vancomycin-loaded chitosan/polyvinyl alcohol (PVA) as the shell. Electron microscopy (SEM and TEM) images confirmed the preparation of smooth, bead-free, and continuous fibers that formed clear core-shell structures. For further studies, nanofiber mats were cross-linked by heat treatment to avoid rapid disintegration in water and improve both mechanical properties and drug release. The release profile of curcumin and vancomycin indicated an initial burst release, continued by the extended release of both drugs within 72 hours. Rabbit corneal cells demonstrated high rates of proliferation when evaluated using a cell metabolism assay. Finally, the therapeutic efficiency of core/shell nanofibers in healing cornea alkali burn was studied by microscopic and macroscopic observation, fluorescence staining, and hematoxylin-eosin assay on rabbit eyes. The anti-inflammatory activity of fabricated fibers was evaluated by enzyme-linked immunosorbent assay and Immunofluorescence analysis. In conclusion, using a robust array of in vitro and in vivo experiments this study demonstrated the ability of the dual-drug carriers to promote corneal re-epithelialization, minimize inflammation, and inhibit corneal neovascularization. Since these parameters are critical to the healing of corneal wounds from alkali burns, we suggest that this discovery represents a promising future therapeutic agent that warrants further study in humans.

Orbital histiocytosis and fibrohistiocytosis: the clinicopathological characteristics of 117 patients, over a decade of experience.

PURPOSE: To describe the clinicopathological features of a large cohort of patients with orbital histiocytoses and fibrohistiocytosis, such as Langerhans cell histiocytosis (LCH) and non-LCH disorders, and correlate patients' clinical characteristics with their pathological diagnosis. METHODS: In this retrospective study, medical records of patients presenting to Farabi Eye Hospital, a tertiary eye care center in Tehran, Iran, from 2010 until 2022, were reviewed. Patients' demographics, chief complaint, location and laterality of the tumor, best-corrected visual acuity, presence of bone erosion on imaging, and their pathological diagnosis were retrieved. Excisional biopsy was performed and evaluated through light microscopy and immunohistochemistry study for their respective markers, including CD1a, CD68, CD207, and S100. RESULTS: A total of 117 patients with 11 pathological subtypes of histiocytoses and fibrohistiocyosis were identified, with 56.4% male and 43.6% female patients. The mean age at presentation was 23.4 years (range 1.5 months-73 years). Swelling and palpable mass were the most common chief complaints. LCH was the most common pathology (32.5%), followed by juvenile xanthogranuloma (26.5%) and adult xanthogranuloma (21.4%). Age, lesion location, and bone erosion had a statistically significant difference among the various diagnosed subtypes. CONCLUSIONS: Histiocytoses and fibrohistiocytosis are diverse and rare disorders potentially involving multiple organ systems. Ophthalmic manifestations of these diseases are even more uncommon. We reviewed their orbital presentation along with their respective histopathological findings. Our results also suggested that an orbital CT scan can be of diagnostic value to discriminate LCH from other histiocytic pathologies.

A rare presentation of orbital spindle cell carcinoma a case report and brief review of the literature.

BACKGROUND: To describe a case of orbital spindle cell carcinoma which presented with limbal ischemia and briefly review the literature. METHODS: Retrospective case report and brief literature review. RESULTS: A 61-year old man presented with blepharoptosis, periorbital pain, decreased vision and limbal ischemia. He did not mention any previous illness and did not take any kind of drugs. Imaging revealed an orbital mass that was positive for SMA, Vimentin and CD99 and negative for S100. We treated the patient with chemotherapy and followed him for other complications that occurred throughout disease course. CONCLUSION: Spindle cell carcinomas are a rare variant of squamous cell carcinoma (SCC) with dual malignant histologic differentiation of squamous and mesenchymal cells. Few cases of orbital spindle cell carcinoma have been reported, which have been either secondary to distant metastasis or regional spread. In this study, we have reported the first case of primary orbital spindle cell carcinoma presenting with limbal ischemia. Further studies are needed to describe the different clinical presentations and management strategies of this rare clinical entity.

Alveolar soft part sarcoma of the superior rectus muscle: Case report and review of literature.

Purpose: Alveolar soft part sarcoma (ASPS) is a very rare type of soft tissue sarcomas which usually occurs in the limbs and trunk. Observations: A 25-year-old woman presented with proptosis and redness of the right eye for 8-month. She suffered from severe right upper lid edema, conjunctival chemosis, downward displacement of the globe, and proptosis. Radiological imaging was nonconclusive. Histopathological evaluations confirmed ASPS. The patient underwent exenteration as a lifesaving procedure. At 16-month follow-up, the patient is stable without any signs of recurrence or metastasis. Conclusions and importance: We report an extremely rare case of ASPS occurring in the superior rectus muscle. Few orbital ASPS cases have been reported in the literature. A literature review of orbital ASPS was done to shed lights on the diagnosis and management of this rare tumor.

Delayed-onset ligneous conjunctivitis as a rare association with congenital hydrocephalous: a case report and review of the literature.

Ligneous conjunctivitis is an uncommon form of chronic and recurrent conjunctivitis characterized by a thick, "woody," yellowish pseudomembranous lesion on the tarsal conjunctiva. Plasminogen deficiency plays an important role in this disease, which affects the mucous membranes, including the conjunctiva as well as other systemic organs. In rare cases, congenital hydrocephalus is associated with this disease. We present the case of a 21-year-old woman with delayed-onset bilateral ligneous conjunctivitis and a history of congenital hydrocephalous in infancy. She was treated with topical ophthalmic medication and surgical excision.

Isolated Intraconal Meningioma.

PURPOSE: To report a rare case of isolated intraconal meningioma. CASE REPORT: A 24-year-old woman presented with painless proptosis in her left eye which started and progressed during her pregnancy about 10 months ago. Hertel exophthalomometry revealed anterior displacement of the globe with 4 mm of proptosis which was remarkable. Magnetic resonance imaging (MRI) demonstrated an intraconal circumscribed oval-shaped mass with hypointense signals on T1-weighted images and hyperintense signals on T2-weighted images, mimicking cavernous hemangioma. This mass, however, was free of any connections to optic nerve or bones. Due to the imaging characteristics, more prevalent diagnoses like cavernous hemangioma were placed on the top of the differential diagnoses list. However, during the surgical excision, the tumor's consistency and gross features were not compatible with cavernous hemangioma. The pathologic findings instead determined meningotheliomatous meningioma, a very rare condition, which was far from our expectations prior to the surgery. CONCLUSION: Ectopic orbital meningiomas are rare tumors that are not easily diagnosed without postoperative histopathology. Despite its low prevalence, they should be considered in the differential diagnosis list of intraconal masses with hypointense signals on T1-weighted images and hyperintense signals on T2-weighted images.

Orbital myiasis on recurrent undifferentiated carcinoma in the COVID-19 era: a case report and brief review of the literature.

BACKGROUND: Myiasis is defined as the infestation of living tissues by Diptera larvae. Ophthalmic involvement occurs in less than 5% of cases. As the most uncommon type of involvement, orbital myiasis usually affects patients with poor personal hygiene, a low socioeconomic status, a history of surgery, and cancer. FINDINGS: In January 2020, an 89-year-old man presented to the Oculoplastic Department of Farabi Eye Hospital (Iran) with a history of left-side progressive orbital mass for six months. A large infiltrative mass of the left orbit with extension to the globe, periorbita, and adnexa was remarkable at the presentation, and its appearance suggested malignancy. Our findings persuaded us to perform exenteration and histopathological evaluation which were reported as "undifferentiated carcinoma". Regular follow-up visits were recommended. In June 2020, with a 3-month delay, the patient presented with the recurrence of the mass complicated with mobile alive larva. Examinations revealed numerous maggots crawling out of an ulcerative and foul-smelling lesion. He stated that fear of COVID-19 infection postponed his follow-up visit. The patient underwent immediate mechanical removal of larvae, followed by wide local excision of the mass. CONCLUSION: Patients with carcinoma of the adnexal tissues seem to be more prone to myiasis infestation even though it is an uncommon disease. Since COVID-19 is an ongoing pandemic with no end in sight appropriate protocols should be implemented to prevent loss of follow-up in these high risk patients.

Safety evaluation of the atmospheric low-temperature plasma (ALTP) on the conjunctiva: an animal study and histopathological findings; 6-month follow-up.

BACKGROUND: Plasma medicine is an innovative research field focused on the application of atmospheric-pressure low-temperature plasmas (ALTP) for therapeutic purposes. Considering the potentials of plasma in ophthalmology, in this study, we evaluated the safety of plasma on the conjunctival tissue in animal models for 6 months. METHODS: Twelve adult male New Zealand albino rabbits were divided into four groups. The right eye of each rabbit was chosen for the test and the left eye was considered as the control. Experiments were performed using the Plexr device (GMV, Rocca Priora, RM, Italy). Four plasma spots were applied on the superior part of the conjunctiva (from 10 to 2 o'clock positions) using the continuous mode and a low power level (white handpiece) of the Plexr. For evaluation of the plasma safety, the histopathological changes were assessed 1 week (A), 1 month (B), 3 months (C), and 6 months (D) after the intervention. RESULTS: According to the histopathological findings, a mild decrease in blood vessels and severe stromal edema, as well as a superficial epithelium loss, were observed in group A. No chronic inflammation, scar tissue, deposition, and hemorrhage were found in group B. Epithelialization was confirmed by the histological examinations after 1 month. There was no evidence of atypia or dysplasia after 3 and 6 months. CONCLUSION: In conclusion, there were no persistent histopathological changes on conjunctival tissue after plasma exposure. Then, plasma can be considered as a minimally invasive alternative method for treating some ocular surface disorders.

Efficacy of topotecan nanoparticles for intravitreal chemotherapy of retinoblastoma.

Retinoblastoma (Rb) is the most common intraocular malignancy in children that accounts for approximately 4% of all pediatric malignancies. Since chemotherapy is a widely practiced treatment for Rb, there is a growing interest in developing new and effective drugs to overcome systemic and local side effects of chemotherapy to improve the quality of life and increase the chances of survival. This study sought to fabricate thiolated chitosan nanoparticles containing topotecan (TPH-TCs-NPs) with a view of enhancing drug loading and release control. This research was also designed to assess the ability of TPH-TCs-NPs to improve cell association, increase treatment efficacy in retinoblastoma cells and xenograft-rat-model of retinoblastoma, and overcome current topotecan hydrochloride (TPH) intravitreal administration challenges, including stability loss and poor cellular uptake. Modified ionic gelation method was optimized to fabricate TPH-TCs-NPs and TPH-TMC-NPs (N-trimethyl chitosan nanoparticles containing TPH). We characterized the NPs and quantified topotecan loading and release against a free TPH standard. The efficacy of TPH-NPs was quantified in human retinoblastoma cells (Y79) by XTT and flow cytometry measurement. In addition, Y79 cells were injected intravitreally in both eyes of immunodeficient wistar albino rats to create a xenograft-rat-model to compare the antitumor effectiveness of TPH-NPs and TPH by intravitreal administration. TPH-NPs complexation was confirmed by EDX, FTIR, and DSC techniques. TPH-TCs-NPs and TPH-TMC-NPs had high encapsulation efficiency (85.23 ± 2 and 73.34 ± 2% respectively). TPH-TCs-NPs showed a mean diameter, polidispersity index, and zeta potential of 25±2 nm, 0.21 ± 0.03 and +12 ± 2 mV, respectively. As a function of dose, TCs and TMC NPs were more efficacious than free topotecan (IC50s 53.17 and 85.88 nM, relative to 138.30 nM respectively, P = 0.012). Kruskal-Wallis test showed a statistically significant difference between the groups. Additionally, a significant difference between the tumor control and TPH-TCs-NPs treated group in xenograft-rat-model ( Range of P-value: 0.026 to 0.035) was shown by Bonferroni post hoc test. The current investigation demonstrated enhanced efficacy and association of TPH-TCs-NPs relative to free TPH in retinoblastoma cells and tumor in vitro and in vivo.

Fabrication, Optimization, and In Vitro and In Vivo Characterization of Intra-vitreal Implant of Budesonide Generally Made of PHBV.

Drug delivery to vitreous in comparison with drug delivery to the other parts of the eye is complicated and challenging due to the existence of various anatomical and physiological barriers. Developing injectable intra-vitreal implant could be beneficial in this regard. Herein, poly(hydroxybutyrate-co-valerate) (PHBV) implants were fabricated and optimized using response surface method for budesonide (BZ) delivery. The acquired implants were characterized in regard to the stability of the ingredients during fabrication process, drug loading amount, and drug release pattern (in PBS-HA-A and in vitreous medium). According to this research and statistical analysis performed, first HV% (hydroxyvalerate) then molecular weight and ratio of PEG as pore former affect respectively release rate and burst strength of BZ with different coefficients. Drug release profile in rabbit eye correlated well with that of in vitro (R2 = 0.9861, p Ë‚ 0.0001). No significant changes were seen in ERG waves, intraocular pressure, and histological studies during the in vivo part of the project. Using 8% HV, 20% PEG/PHBV, and higher molecular weight PEG (i.e., 6000), the optimum formulation was achieved. Toxicity and biocompatibility of the optimized formulation, which were evaluated in vivo, indicated the suitability of design implant for intra-vitreal BZ delivery. Grapical abstract.

Safety of Intravitreal Injection of Stivant, a Biosimilar to Bevacizumab, in Rabbit Eyes.

PURPOSE: To evaluate the safety of intravitreal injection of Stivant, a biosimilar to bevacizumab, in rabbits using electrophysiological and histological analysis. METHODS: Both eyes of 41 New Zealand albino rabbits were injected with 0.1 mL (2.5 mg) of Stivant. The rabbits were scheduled to be sacrificed 1, 2, 7, 14, and 28 days after injection for histopathological evaluations. Clinical examinations and electroretinography (ERG) were performed at baseline and just before sacrificing the rabbits. Fourteen separate rabbits received a reference drug (Avastin) and were considered as the control group. Furthermore, three other rabbits received the same volume of saline (saline control group). Rabbits of both control groups were sacrificed four weeks after injection. ERG was performed 1, 2, 7, 14, and 28 days after injections. RESULTS: No significant difference was observed in a- and b-wave amplitudes and latency after intravitreal Stivant injection between baseline and different time points. Moreover, there was no statistically significant difference in wave amplitudes and latency between the Stivant and control groups. The histology of rabbit eyes of the Stivant and control groups after intravitreal injections was not distinguishable. CONCLUSION: The biosimilar Stivant, up to a dose of 2.5 mg, did not appear to be toxic to the retina in albino rabbits. These results suggest that this drug could be a safe and inexpensive alternative to intravitreal bevacizumab. The efficacy of these injections was not investigated in this study and needs to be evaluated in future studies.

Safety of Intravitreal Injection of Biosimilar of Aflibercept in Rabbit Eyes.

PURPOSE: To assess the safety of biosimilar intravitreal aflibercept (CinnaGen Co., Iran) compared to the reference product (Eylea®; Bayer Schweiz AG, Zurich, Switzerland) in rabbit eyes through functional and histologic studies. METHODS: Forty New Zealand albino rabbits were recruited to the study and were divided into four groups to be sacrificed at 48 hours, one, two, and four weeks after injections. In each group, five rabbits received 0.05 mL (2 mg) biosimilar aflibercept in the right eye and 0.05 mL saline in the left eye as the control, and in a similar manner, the remaining five rabbits received the reference drug in the right eye and saline in the left eye. All the rabbits underwent comprehensive ophthalmic examination and electroretinography (ERG) tests at baseline and also just before enucleation at the specific predefined time points. The enucleated eyes were prepared for retinal toxicity histological examination. RESULTS: No retinal toxicity was observed based on histologic and ERG findings in all groups. Choroidal congestion was revealed after 1 week in an eye that was injected with biosimilar aflibercept, although the similar finding was detected in the contralateral eye which received saline. Also, one subject which received the reference drug showed chronic vitritis and lymphoplasmocytic reaction of the optic disc at week 4. The remaining subjects showed no histologic changes. CONCLUSION: The 2 mg intravitreal injection of biosimilar aflibercept (CinnaGen Co., Iran) was found to be nontoxic in rabbit eyes in the short-term period. Further studies are required to warrant the efficacy and safety profile of the drug in human subjects.

Giant Cell Tumor: Changing Behavior from Intraorbital to Intraosseous Mass.

PURPOSE: To present a patient with giant cell tumor (GCT) of the orbit by changing behavior from an intraorbital mass to an intraosseous tumor. METHODS: A 16-year-old boy presented with pain, swelling, erythematous of the left upper and lower eyelids, proptosis, and diplopia. Ophthalmic examination revealed chemosis, conjunctival injection, limited elevation, depression as well as abduction in the left eye. RESULTS: Multislice computed tomography scan (CT scan) of the orbit and paranasal sinuses showed a hyperdense, oval, extraconal mass with bone erosion. Magnetic resonance imaging of the orbit showed an inferior lateral isointense, oval, extraconal mass that had indented the globe. The patient underwent superior lateral orbitotomy, and the orbital mass was excised. Two months later, the patient developed proptosis, severe chemosis, and eyelid erythema in the same eye. CT scan showed an intraosseous mass in the lateral wall of the orbit that had pushed the globe anteromedially. Intraosseous tumor was resected, and the lateral orbital wall was drilled during the second surgery. GCT was diagnosed based on pathological survey. CONCLUSION: Following the resection of the orbital GCT, the tumor behavior may change to an intraosseous lesion.

Long term features of diabetic retinopathy in streptozotocin-induced diabetic Wistar rats.

Diabetic retinopathy is a complication of diabetes and a leading cause of vision loss among working-age adults. To assess whether the Wistar rat with Streptozotocin (STZ)-induced diabetes is a suitable animal model of human proliferative diabetic retinopathy we evaluated the vascular changes to assess the diabetic retinopathy (DR) stages in this model. After two weeks of intraperitoneal STZ (55 mg/kg) injection in male Wistar rats (270-300 g), they were considered diabetic with persistent blood glucose levels ≥ 16.65 mmol/L. The diabetic and control rats were investigated after 1, 3, 6 and 9 months by electroretinography, Evans blue assay, dextran fluorescence retinal angiography, and retinal histopathological studies. Retinal vascular permeability in the diabetic groups increased significantly in all diabetic groups. The amplitude of a- and b-waves decreased significantly in all diabetic groups compared with the age-matched control groups. The latent time of a-waves in the diabetic groups was delayed at 3 months of diabetes and this delay remained relatively constant till 9 months following the onset of diabetes. Although the latent time of b-wave in the diabetic groups increased slightly, a significant difference was found right at 9 months of diabetes. Vascular density and branching point numbers significantly decreased in the diabetic eyes at 3 and 6 months while they increased at 9 months, which was not significant. Intraretinal hemorrhage and ischemic changes were detected in the half of diabetic rats after 6 months and considered as preproliferative stage of diabetic retinopathy. Although preproliferative changes were detected in all diabetic rats at 9 months, half of them showed vitreous neovascularization attached to retina and retinal folds which can be considered as proliferative stage of DR. Intraretinal hemorrhage, extensive leakage of fluorescein, retinal folds, and vitreous neovascularization were the most prominent findings of severe and proliferative diabetic retinopathy in a fraction of the STZ-induced diabetic rats which were comparable to that of the human patients. STZ-induced diabetic rats can be considered to be a potentially useful model for studies on pathogenesis and treatment of diabetic retinopathy in human.

Genetic features of Pseudomonas aeruginosa isolates associated with eye infections referred to Farabi Hospital, Tehran, Iran.

BACKGROUND: Pseudomonas is the most common cause of microbial keratitis especially in people who use contact lens. The virulence of Pseudomonas aeruginosa in different eye infections is associated with different virulence factors . METHODS: In this study, 54 P. aeruginosa isolates including 39 isolates from keratitis and 15 isolates from conjunctivitis were evaluated for their ability to form biofilm, production of protease, elastase, alkaline protease and their antibiotic-resistant patterns. The distribution of the exoS and exoU genes in the test strains were determined using PCR assays. RESULTS: Most of the eye infections (90.74%) were seen in people who used contact lenses, and in most of patients (72.22%), the infection was presented as keratitis. None of the isolates were resistant to a single antibiotic as tested. Multidrug resistance (MDR) was detected in two isolates (3.5%) which were resistant to more than one category of antibiotics. The exoU+/exoS+ isolates were in majority although in total, compared to exoS, there were more exoU in a greater number of samples. Most of the strains produce elastase but among all of ocular isolates, only 5.8% of the strains showed alkaline protease activity. Most of the ocular isolates were not capable of producing biofilm. CONCLUSIONS: In our study, a high prevalence of virulence factors was observed in P. aeruginosa isolates from contact lens wearer with keratitis. As the P. aeruginosa isolates from different infection origins and different geographic region may have different virulence factors, having a better perception of these differences could help to improve development of clinical instructions for the control of keratitis.

Different Genotypes of Adhesion Operon Genes in Staphylococcus epidermidis Isolates From Various Ocular Infections.

BACKGROUND: Staphylococcus epidermidis is one of the common causes of bacterial keratitis and post-operation infections. One of the most important virulence factors of S. epidermidis is biofilm formation. Poly-N-acetylglucosamine (PNAG) production is critical for biofilm formation in S. epidermidis. The intercellular adhesion (ica) operon is formed by icaA, icaD, icaB, and icaC genes, which participate in the biosynthesis of PNAG. Strains of S. epidermidis from different infections show different genotypes in relation to adhesion operon genes. Therefore, regarding the fact that the pathogenic strain in each community has unique genotypes, this study investigated the relation between ica operon genotypes and various ocular infections. However, the correlation between the ica operon genes and the mecA gene was analyzed in the isolates. METHODS: For this study, samples of the conjunctiva, cornea, and intraocular fluid of patients with ocular infection were collected. After culture and incubation, detection of S. epidermidis was performed using biochemical and coagulase tests. The antibiotic susceptibility of the bacteria was evaluated by the disk diffusion method. After this, DNA was extracted from the bacteria and the presence of icaA, icaD, is256, and mecA genes was analyzed using polymerase chain reaction. RESULTS: All 50 coagulase-negative Staphylococcus samples isolated from different eye infections were characterized as S. epidermidis. Most of the samples (36%) were isolated from the cornea and the others were, respectively, from the conjunctiva (24%), vitreous (20%), anterior chamber (8%), eyelid (6%), and nasolacrimal duct (6%). The icaA, icaD, and is256 genes were detected with different genotypes in isolates from keratitis and endophthalmities compared with conjunctivitis. Overall, the most isolated genotype from ocular infections was icaA+. icaD+. is256+. (46%). Most of the isolates (82.60%) had mecA, icaA, and icaD genes simultaneously, which indicates a strong relationship between the adhesion genes and the antibiotic resistance gene. CONCLUSIONS: The adhesion operon genes were observed with different genotypes in S. epidermidis samples isolated from various ocular infections.

Malignant peripheral nerve sheath tumor of lacrimal nerve: a case report.

BACKGROUND: Orbital and periorbital presentation is rare for malignant peripheral nerve sheath tumors. These tumors are poorly defined spindle cell neoplasms of peripheral nerves and have not been reported to develop in the lacrimal gland to date. AIM: To report a rare presentation of malignant peripheral nerve sheath tumor in the orbital cavity. CASE REPORT: A 65-year-old man was admitted with the chief complaint of prominent right eye. His symptoms began 16 months prior to his admission. He had obvious limited ocular motion in upgaze and lateral gaze directions, as well as diplopia in all directions. He underwent imaging studies, and an iso-dense mass lesion in the lacrimal gland was revealed in orbital CT scan. In the MRI, there was a well-defined iso-intense mass lesion in T1-weighted images that was hyperintense in T2-weighted images and was enhanced with Gadolinium. Excisional biopsy revealed epithelioid and spindle cells with hyperchromatic rather than pleomorphic nuclei. Immunohistochemistry confirmed the presence of positive markers consistent with malignant peripheral nerve sheath tumor. CONCLUSION: Malignant peripheral nerve sheath tumor should be considered in the differential diagnosis of lacrimal gland tumors. Imaging studies may be helpful but tissue biopsy should be performed for accurate diagnosis. Complete excision of the mass lesion and adjunctive chemotherapy and radiotherapy should be considered in these cases.

Orbital metastasis: a rare manifestation of scapular bone osteosarcoma.

PURPOSE: To report a case of orbital metastasis from scapular bone osteosarcoma. CASE REPORT: A 55-year-old man who was a known case of scapular bone osteosarcoma, was referred to our clinic with ocular symptoms including acute painful decreased vision, proptosis, conjunctival injection, and chemosis. He had undergone surgical excision of the original tumor and received systemic chemotherapy 4 months before. Imaging studies and incisional biopsy were performed for the orbital lesion, the histopathological examination confirmed the diagnosis of metastatic osteosarcoma. The patient was referred to the oncologist for palliative chemotherapy and further intervention; however, he deceased 2 months later due to sepsis in the context of immunosuppression. CONCLUSION: Metastatic involvement of the orbit due to osteosarcoma is a rare condition manifesting with orbital mass, pain, diplopia and ocular motility disturbance. Although there is no effective treatment, the combination of modalities such as chemotherapy, radiotherapy, and surgery may delay progression of the disease.

Pathological findings in enucleated eyes after intravitreal melphalan injection.

The aim of this study is to evaluate the pathological findings of the eye after intravitreal melphalan for viable vitreous seeding from retinoblastoma. All enucleated eyes receiving an intravitreal injection of melphalan (10-50 µg in 0.05 cc) were evaluated for histological changes. Of 25 treated cases, 8 eyes needed enucleation because of phthisis, parent request, or new tumor development. One of the cases was excluded from the study because of a history of intra-arterial chemotherapy with melphalan. There was no case of needle-site scleral involvement by retinoblastoma cells. In two eyes receiving 50 µg melphalan, no viable retinoblastoma cell was detectable in the eye. Severe gliosis, vascular occlusion, retinal necrosis, hemorrhage and neovascularization were seen. Histologically, intravitreal melphalan for recalcitrant or recurrent vitreous seeds from retinoblastoma appears to provide acceptable vitreous seed control. It seems that higher doses could be destructive causing ischemic necrosis in the retina, severe gliosis and secondary neovascular changes as well as having a destructive effect on retinoblastoma cells.