Does Multimodal Treatment Improve Eye and Life Salvage in Adenoid Cystic Carcinoma of the Lacrimal Gland?

PURPOSE: To evaluate the efficacy of multimodal treatment in adenoid cystic carcinoma (ACC) of the lacrimal gland. METHODS: A retrospective comparative case series of 40 consecutive patients with ACC of the lacrimal gland without systemic metastasis at the initial presentation and primarily managed by one of the 3 treatment protocols-surgery + external beam radiotherapy (EBRT) (group 1), surgery + EBRT + adjuvant chemotherapy (group 2), and neoadjuvant chemotherapy + surgery + EBRT + adjuvant chemotherapy (multimodal treatment) (group 3) at a tertiary care ocular oncology center. Local tumor control, eye salvage, and systemic metastasis were the primary outcome measures. RESULTS: The age ranged from 11 to 72 (mean ± SD, 36 ± 13; median, 36) years with 26 (65%) male and 14 (35%) female patients. Twelve (30%) patients belonged to group 1, 8 (20%) to group 2, and 20 (50%) to group 3. Primary surgery included tumor excision in 36 (90%) and orbital exenteration in 4 (10%). Chemotherapy composed of cisplatin + 5 fluorouracil (5FU) for 6 cycles in 28 (70%) patients. Extended-field stereotactic EBRT with a dose of 5,000-6,000 cGy included the entire pretreatment extent of the tumor with a 10-mm margin all around, superior orbital fissure, inferior orbital fissure, cavernous sinus, and temporal fossa. Mean duration of follow up after completion of treatment was 58 ± 26 (range, 29-180; median, 60) months. In all, local tumor recurrence occurred in 10 (25%) patients at a mean of 38 ± 23 (range, 12-120; median, 24) months. Local tumor recurrence was noted in 5 (42%) patients in group 1, 2 (25%) in group 2, and 3 (15%) in group 3. Overall, eye salvage was possible in 34 (85%) patients, with visual acuity >20/40 in 28 (82%). Systemic metastasis occurred in 10 (25%) patients at a mean of 53 ± 28 (range, 12-120; median, 43) months. Eight (67%) patients in group 1, 1 (13%) in group 2, and 1 (5%) in group 3 developed systemic metastasis. Six (15%) overall, 5 (42%) in group 1 and 1 (13%) in group 2, died with systemic metastasis. CONCLUSIONS: Multimodal treatment with sequential neoadjuvant chemotherapy, followed by surgery, extended-field stereotactic EBRT, and adjuvant chemotherapy seems relatively more effective in providing local tumor control and eye salvage and in minimizing the risk of systemic metastasis in ACC of the lacrimal gland.

Isolated intraosseous extra-gnathic orbital myxoma: a clinicopathologic case report.

A 19-year-old female student presented with painless, progressive proptosis in the right eye for the past six months causing significant cosmetic blemish and double vision. Clinical evaluation revealed normal visual acuity, normal pupillary reflex, severe proptosis, and dystopia. Orbital imaging revealed a heterogeneous mass in superior orbit displacing the globe inferiorly and causing extensive bony erosion of frontal bone superiorly and invading the frontal sinus. Excision biopsy was performed with en-bloc removal of the tumor. Surgical delivery of a slimy mass with infiltrated bony tissue led to a presumptive diagnosis of myxoid liposarcoma. Careful histopathologic analysis coupled with immunohistochemical studies were performed which established the rare diagnosis of low-grade myxoid spindle cell neoplasm with features suggestive of intraosseous myxoma. On follow-up at 15 months, our patient revealed no signs of recurrence. Isolated intraosseous orbital myxoma is a rare entity; only two such cases have been reported in the literature.

Diffuse Anterior Retinoblastoma with Globe Salvage and Visual Preservation in 3 Consecutive Cases.

PURPOSE: Diffuse anterior retinoblastoma is an exquisitely rare variant of retinoblastoma in which the tumor resides in the anterior segment of the eye, without apparent retinal involvement. Previously published cases have been managed with enucleation. We describe globe salvage and visual preservation in 3 consecutive cases using chemotherapy and radiotherapy. DESIGN: Retrospective case series. PARTICIPANTS: Three children with diffuse anterior retinoblastoma. METHODS: Plaque radiotherapy plus intravenous chemotherapy. MAIN OUTCOME MEASURES: Globe and vision preservation. RESULTS: The mean patient age at presentation elsewhere was 5.7 years (median, 7; range, 3-7 years). There were 2 white female patients and 1 African American male patient. The initial observation by parents/caregiver was reduced vision (n = 1), red eye (n = 1), or cloudy eye (n = 1), and the initial finding by physician was iris tumor (n = 2) or hyphema (n = 1). Referring diagnosis was iris melanoma (n = 1), infectious endotheliitis (n = 1), and possible tumor (nonspecified) (n = 1). At our evaluation, visual acuity was 20/50 to 20/60 (n = 2) and fix no follow (n = 1). In all cases, the opposite eye was normal. Mean intraocular pressure was 20 mm Hg (median, 16; range, 15-30 mmHg). Our examination revealed solid iris tumor (n = 3), ciliary body involvement (n = 2), and anterior chamber seeding (n = 3). In no case was there choroidal or retinal tumor, vitreous seed or subretinal seed, or extrascleral extension. Clear corneal fine-needle aspiration biopsy confirmed the diagnosis as retinoblastoma in each case. Treatment included plaque radiotherapy (n = 3) plus additional systemic chemotherapy (n = 2). At mean follow-up of 35 months (median, 34; range, 20-51 months), there has been no recurrence, extrascleral extension, enucleation, metastasis, or death. In all 3 cases, cataract surgery was necessary at a mean interval of 16 months after complete and stable regression of retinoblastoma. CONCLUSIONS: The rare diffuse anterior form of retinoblastoma can be managed with globe-salvaging alternatives and with visual preservation in selected cases.

Management and outcome of retinoblastoma with vitreous seeds.

PURPOSE: To report the treatment response of retinoblastoma with vitreous seeds to high-dose chemotherapy coupled with periocular carboplatin. DESIGN: Retrospective, interventional case series. PARTICIPANTS: Consecutive patients with retinoblastoma with vitreous seeds managed over 10 years at a comprehensive ocular oncology center and followed up for at least 12 months after the completion of treatment were included in this study. Institutional review board approval was obtained. INTERVENTION: High-dose chemotherapy with a combination of vincristine, etoposide, and carboplatin in patients with focal vitreous seeds and additional concurrent periocular carboplatin in patients with diffuse vitreous seeds. MAIN OUTCOME MEASURES: Tumor regression, vitreous seed regression, and eye salvage. RESULTS: After excluding the better eye of bilateral cases, 101 eyes of 101 patients were part of the final analysis. All the patients belonged to Reese-Ellsworth group VB, but on the International Classification of Retinoblastoma (ICRB), 21 were group C, 40 were group D, and 40 were group E. The mean basal diameter of the largest tumor was 11.8 ± 4.7 mm. Mean tumor thickness was 7.5 ± 4.0 mm. Vitreous seeds were focal in 21 eyes and diffuse in 80 eyes. Chemotherapy cycles ranged from 6 to 12 (median, 6). Seventy-three eyes with diffuse vitreous seeds received a 15-mg posterior sub-Tenon carboplatin injection (range, 1-13 mg; median, 6 mg). Follow-up duration ranged from 13.4 to 129.2 months (median, 48 months). External beam radiotherapy (EBRT) was necessary in 33 eyes with residual tumor, vitreous seeds, or both. In all, 20 eyes (95%) with ICRB group C retinoblastoma, 34 eyes (85%) with group D retinoblastoma, and 23 eyes (57.5%) with group E retinoblastoma were salvaged. Of 77 eyes that were salvaged, 74 (96%) had visual acuity of 20/200 or better. Twenty-four of 33 chemotherapy failures (73%) regressed with EBRT. None of the patients demonstrated second malignant neoplasm or systemic metastasis. Factors predicting tumor regression and eye salvage were bilateral retinoblastoma and absence of subretinal fluid. Factors predicting vitreous seed regression were absence of subretinal fluid and subretinal seeds. CONCLUSIONS: Intensive management with primary high-dose chemotherapy and concurrent periocular carboplatin, and EBRT selectively in chemotherapy failures, provides gratifying outcome in retinoblastoma with vitreous seeds.

Intra-arterial chemotherapy for retinoblastoma in 70 eyes: outcomes based on the international classification of retinoblastoma.

OBJECTIVE: To analyze our 5-year experience of intra-arterial chemotherapy (IAC) for retinoblastoma as primary or secondary therapy. DESIGN: Retrospective interventional case series. PARTICIPANTS: A total of 70 eyes of 67 patients. INTERVENTION: Ophthalmic artery chemotherapy infusion under fluoroscopic guidance was performed using melphalan (3, 5, or 7.5 mg) in every case, with additional topotecan (1 mg) and/or carboplatin (30 or 50 mg) as necessary. MAIN OUTCOME MEASURES: Tumor control and treatment complications. RESULTS: The mean patient age at IAC was 30 months. The treatment was primary in 36 eyes and secondary in 34 eyes. Those primary therapy eyes were classified according to the International Classification of Retinoblastoma (ICRB) as group A (n = 0), B (n = 1), C (n = 4), D (n = 17), or E (n = 14). The secondary therapy eyes had failed previous intravenous chemotherapy (n = 34) in every case. Each eye received a mean of 3 IAC sessions per eye (median, 3; range, 1-7 sessions). After IAC with a mean follow-up of 19 months, globe salvage was achieved in 72% of primary-treated cases and in 62% of secondary-treated cases. Specifically, primary therapy achieved globe salvage for group B (100%), group C (100%), group D (94%), and group E (36%). Of all 70 eyes, complete regression was achieved for solid tumor in 48 of 51 eyes (94%), subretinal seeds in 40 of 42 eyes (95%), and vitreous seeds in 34 of 39 eyes (87%). After each catheterization (n = 198), the main complications included transient eyelid edema (5%), blepharoptosis (5%), and forehead hyperemia (2%). More lasting complications included vitreous hemorrhage (2%), branch retinal artery obstruction (1%), ophthalmic artery spasm with reperfusion (2%), ophthalmic artery obstruction (2%), partial choroidal ischemia (2%), and optic neuropathy (<1%). Over the past 3 years, the combined incidence of ophthalmic, retinal, and choroidal vascular ischemia was reduced to 1%. There was no patient with stroke, seizure, neurologic impairment, limb ischemia, secondary leukemia, metastasis, or death. CONCLUSIONS: Five-year experience with IAC indicates that this technique is remarkably effective for the management of retinoblastoma as both a primary and a secondary treatment.

Cryotherapy-induced release of epiretinal membrane associated with retinal vasoproliferative tumor: analysis of 16 cases.

PURPOSE: To evaluate epiretinal membrane (ERM) response after cryotherapy for retinal vasoproliferative tumors (VPTs). METHOD: Retrospective interventional case series. RESULTS: Of 16 eyes with VPT and ERM, the tumor was classified as primary in 12 (75%) eyes or secondary in 4 (25%) eyes. The median patient age was 44 years (mean, 43 years; range, 9-70 years). The tumor was located in extramacular zone (n = 16, 100%) and inferotemporal quadrant (n = 12, 75%). The mean tumor base was 6 mm, and thickness was 3 mm. The ERM involved the macula in 12 (75%) eyes and extramacular zone in 4 (25%) eyes, with best-corrected visual acuity of 20/40 or better in 6 (38%) eyes. Associated features included cystoid macular edema (n = 8, 50%), subretinal fluid (n = 10, 63%), vitreous cells (n = 9, 56%), and vitreous hemorrhage (n = 7, 44%). Single-session cryotherapy (double freeze-thaw) to the VPT was performed in each case. Over mean follow-up of 68 months (median, 54 months; range, 8-252 months), tumor regression was documented in 16 (100%) cases, with ERM release in 10 (63%) cases. After ERM release, the foveal anatomy was normal in 12 (75%) eyes. Final visual acuity improved (n = 5, 31%), remained stable (n = 9, 56%), or worsened (n = 2, 13%). Posttreatment best-corrected visual acuity was 20/40 or better in 10 (63%) eyes. CONCLUSION: Cryotherapy is remarkably effective for VPT of 6 mm or less in basal dimension. After cryotherapy, VPT-related ERM spontaneously released in 63% of the cases, without the need for surgical intervention.

Ciliary body medulloepithelioma: analysis of 41 cases.

PURPOSE: To describe the clinical features, histopathology, treatment, and outcomes of ciliary body medulloepithelioma. DESIGN: Retrospective study. PARTICIPANTS: Forty-one patients with medulloepithelioma. INTERVENTION: Cryotherapy, plaque radiotherapy, external beam radiotherapy, tumor removal by partial lamellar sclerouvectomy (PLSU), or enucleation. MAIN OUTCOME MEASURES: Metastasis and death. RESULTS: Of 41 patients with ciliary body medulloepithelioma, the median age at diagnosis was 5 years. The mean tumor basal diameter was 11 mm, and the mean tumor thickness was 7 mm. Related features included secondary glaucoma (n = 18, 44%), iris neovascularization (n = 21, 51%), cataract (n = 19, 46%), lens subluxation (n = 11, 27%), lens coloboma (n = 8, 20%), retrolental neoplastic cyclitic membrane (n = 21, 51%), intratumoral cysts (n = 25, 61%), and extraocular extension (n = 4, 10%). There was systemic association with pleuropulmonary blastoma in 2 cases (5%). Primary tumor treatment included enucleation (n = 21, 60%), tumor removal by PLSU (n = 8, 23%), plaque radiotherapy (n = 3, 9%), external beam radiotherapy (n = 1, 3%), cryotherapy (n = 1, 3%), or palliative chemotherapy (n = 1, 3%). In 1 case, medulloepithelioma was diagnosed histopathologically after inadvertent evisceration for blind painful eye. Subsequent treatment for residual or recurrent tumor in cases treated conservatively/inappropriately (n = 15) was necessary in 7 cases (47%). Histopathology disclosed benign features in 6 cases (20%), malignant features in 24 cases (80%), teratoid features in 11 cases (37%), and nonteratoid features in 19 cases (63%). In the 26 enucleated eyes, other features included retrolental neoplastic cyclitic membrane (n = 18, 69%), neoplastic epiretinal membrane (n = 6, 23%), and persistent hyaloid artery (n = 6, 23%). Systemic metastasis occurred in 3 cases (8%) over a mean follow-up of 49 months, all of whom presented with extrascleral extension of tumor due to mean delay in diagnosis by 39 months. CONCLUSIONS: Medulloepithelioma most commonly occurs in children. Systemic association with pleuropulmonary blastoma rarely is found. Patients with extrascleral medulloepithelioma are at risk for metastasis.

Epidemiology, clinical profile, management, and outcome of COVID-19-associated rhino-orbital-cerebral mucormycosis in 2826 patients in India - Collaborative OPAI-IJO Study on Mucormycosis in COVID-19 (COSMIC), Report 1.

Purpose: COVID-19-associated rhino-orbital-cerebral mucormycosis (ROCM) has reached epidemic proportion during India's second wave of COVID-19 pandemic, with several risk factors being implicated in its pathogenesis. This study aimed to determine the patient demographics, risk factors including comorbidities, and medications used to treat COVID-19, presenting symptoms and signs, and the outcome of management. Methods: This was a retrospective, observational study of patients with COVID-19-associated ROCM managed or co-managed by ophthalmologists in India from January 1, 2020 to May 26, 2021. Results: Of the 2826 patients, the states of Gujarat (22%) and Maharashtra (21%) reported the highest number of ROCM. The mean age of patients was 51.9 years with a male preponderance (71%). While 57% of the patients needed oxygen support for COVID-19 infection, 87% of the patients were treated with corticosteroids, (21% for > 10 days). Diabetes mellitus (DM) was present in 78% of all patients. Most of the cases showed onset of symptoms of ROCM between day 10 and day 15 from the diagnosis of COVID-19, 56% developed within 14 days after COVID-19 diagnosis, while 44% had delayed onset beyond 14 days. Orbit was involved in 72% of patients, with stage 3c forming the bulk (27%). Overall treatment included intravenous amphotericin B in 73%, functional endoscopic sinus surgery (FESS)/paranasal sinus (PNS) debridement in 56%, orbital exenteration in 15%, and both FESS/PNS debridement and orbital exenteration in 17%. Intraorbital injection of amphotericin B was administered in 22%. At final follow-up, mortality was 14%. Disease stage >3b had poorer prognosis. Paranasal sinus debridement and orbital exenteration reduced the mortality rate from 52% to 39% in patients with stage 4 disease with intracranial extension (p < 0.05). Conclusion: : Corticosteroids and DM are the most important predisposing factors in the development of COVID-19-associated ROCM. COVID-19 patients must be followed up beyond recovery. Awareness of red flag symptoms and signs, high index of clinical suspicion, prompt diagnosis, and early initiation of treatment with amphotericin B, aggressive surgical debridement of the PNS, and orbital exenteration, where indicated, are essential for successful outcome.

Ocular oncology practice guidelines during COVID-19 pandemic-An expert consensus.

The outbreak of rapidly spreading COVID-19 pandemic in December 2019 has witnessed a major transformation in the health care system worldwide. This has led to the re-organization of the specialty services for the effective utilization of available resources and ensuring the safety of patients and healthcare workers. Suspension of oncology services will have major implications on cancer care due to delayed diagnosis and treatment leading to irreversible adverse consequences. Therefore various oncology organizations have called for a continuation of cancer care during this crisis with diligence. The COVID-19 pandemic has forced the clinicians to transform the components of care from screening to outpatient care and primary management. The purpose of this article is to establish guidelines and recommendations for ocular oncology in the management of ocular tumors set by a multidisciplinary team of experts including ocular, medical and radiation oncologists, and pathologists. As the pandemic is evolving fast, it will require constant updates and reformation of health strategies and guidelines for safe and quality health care.

Pediatric viral orbital cellulites secondary to H1N1 infection: A case report.

A 10-year-old boy admitted for high-grade fever and pneumonia developed left preseptal and early orbital cellulitis, unresponsive to higher intravenous antibiotics. He received oseltamivir, on testing positive for H1N1 virus on the nasopharyngeal and throat swabs. There was dramatic improvement with resolution of orbital cellulitis within 24 h of starting oseltamivir. We report a very rare presentation of pediatric orbital cellulitis secondary to systemic H1N1 infection. Prompt investigations and timely treatment with oseltamivir aided in complete resolution, avoiding vision and life-threatening complications.

Intra-arterial chemotherapy in retinoblastoma - A paradigm change.

Intra-arterial chemotherapy (IAC), also known as superselective ophthalmic artery chemotherapy or chemosurgery, is currently widely accepted as one of the primary treatment modalities for intraocular retinoblastoma worldwide. Following the introduction of the technique in 1998, IAC has evolved over the past decades to be safer and more effective. Accumulated evidence shows that IAC is more effective in providing eye salvage in group D and E retinoblastoma as compared to conventional systemic intravenous chemotherapy (IVC). In contrast to IVC, IAC has the added benefits of reduced overall treatment duration and minimal systemic toxicity. This review provides a comprehensive update on the history, technique, indications, contraindications, and outcome of IAC. We have also identified the strengths, weaknesses, opportunities and threats (SWOT analysis) of the technique in this review.

In-utero ultrasonography detection of fetal retinoblastoma and neonatal selective ophthalmic artery chemotherapy.

We report a case of non-familial, sporadic fetal retinoblastoma (RB) that was accidently detected at 39 weeks of gestation on pre-natal ultrasonography in left eye (OS). Post-natal examination revealed Group A and, Group D RB in right eye (OD) and OS, respectively. At 35 days, selective ophthalmic artery intra-arterial chemotherapy (IAC) was performed in OS and laser for OD. Pre-natal ultrasound and its application in RB are limited to those cases with a strong genetic predisposition. Our case was accidently detected at late gestation with no familial or genetic predisposition. In addition, this was the youngest reported case that received IAC on literature review.

Recent Advances in Orbital Tumors--A Review of Publications from 2014-2016.

The aim of this review article is to provide an update of the current literature on orbital tumors. The authors conducted a PubMed literature search of English language articles published between January 2014 and December 2016 using the following search items: orbit, tumors, lacrimal gland, lymphoma, hemangioma, lymphangioma. The authors included reviews, original articles, case series, and case reports with relevant new information. There is new information about the clinical spectrum of orbital tumors, capillary hemangioma, cavernous hemangioma, lymphangioma, orbital venous malformation, lacrimal gland tumors, and orbital lymphoma. This review highlights the current understanding, practice, and guidelines in the diagnosis and management of common tumors of the orbit.

Orbital retinoblastoma: An update.

Orbital extension is a major cause of death in children with retinoblastoma in the developing countries. Delayed detection and inappropriate management contribute to poor outcome. Conventional treatment including primary orbital exenteration or chemotherapy or radiotherapy alone result in mortality as high as 70%. The recent understanding on the role of sequential multimodal therapy with a combination of high-dose chemotherapy, followed by appropriate surgery, radiotherapy, and additional adjuvant chemotherapy has helped dramatically improve life salvage.

The role of intravitreal chemotherapy for retinoblastoma.

Targeted therapy in retinoblastoma (RB) is widely accepted as the current management tool with an aim of increasing drug availability at the tumor location. Inevitably the effect is several times higher compared to systemic delivery of chemotherapeutic drugs and carries less systemic toxicity. Despite tremendous advancement in saving life, eye salvage in advanced RB especially with active vitreous seeds remains a challenge. The hypoxic environment of the vitreous and reduced vitreous concentration of the drugs delivered makes these tumor seeds resistant to chemotherapy. Direct delivery of chemotherapeutic drugs into the vitreous cavity aids to overcome these challenges and is progressively being accepted worldwide. However, intraocular procedure in RB was abandoned due to high risk of extraocular tumor dissemination. Recently, the forbidden therapeutic technique was re-explored and modified for safe use. Although eye salvage rate has tremendously improved after intravitreal chemotherapy (IVitC), retinal toxicity, and vision salvage are yet to be validated. In our preliminary report of intravitreal melphalan in 11 eyes, we reported 100% eye salvage and 0% recurrence with an extended 15 months mean follow-up. In this review, we analyzed published reports on IVitC in RB via PubMed, Medline, and conference proceedings citation index, electronic database search, without language restriction that included case series and reports of humans and experimental animal eyes with RB receiving IVitC.

Tumors of the ocular surface: A review.

Tumors of the Ocular Surface clinically manifest with a very wide spectrum and include several forms of epithelial, stromal, caruncular, and secondary tumors. As a group, these tumors are seen commonly in the clinical practice of a comprehensive ophthalmologist, cornea specialist, and an ocular oncologist. This review is aimed to discuss the common tumors of the ocular surface and emphasize on their clinical diagnosis and appropriate management.

Optical coherence tomography characteristics of epi-iridic membrane in a child with recurrent hyphema and presumed juvenile xanthogranuloma.

We report a case of spontaneous hyphema in a 6-month-old girl with no history of trauma and no visible iris mass. Subtle green-blue heterochromia was noted in the right eye. The iris crypts in the right eye appeared flattened by a thin, transparent layer on the iris surface. Anterior segment optical coherence tomography (AS-OCT) disclosed a thin homogenous membrane overlying the entire iris surface in the right eye. Fluorescein angiography revealed diffuse hyperfluorescence without neovascularization. These features were suggestive of diffuse iris juvenile xanthogranuloma. Sub-Tenon's triamcinolone acetate plus topical corticosteroids eyedrops resolved the condition within 1 month.