Variable presentations of six conjunctival/limbal ocular surface squamous neoplasia (OSSN) cases: How good is our clinical judgment evidenced by the correlation to the histopathological findings and diagnosis?

INTRODUCTION: Ocular surface squamous neoplasia (OSSN) may have atypical or unusual presentations and may attain large sizes especially in cases of delayed presentation resulting in late diagnosis, treatment, and eventual guarded visual prognosis. We are reporting an interesting cases series of OSSN with variable clinical presentations to highlight the importance of the pre-operative clinical judgment and tissue diagnosis. PRESENTATION OF CASES: Six patients (4 females and 2 males; mean age 59 years; range 42-79 years) were included with suspicious conjunctival lesions. The maximum dimension of the lesions was 17 mm. The initial suspected pre-operative clinical diagnosis -other than OSSN- included pterygium/pinguecula (n = 2), benign squamous papilloma (n = 1), cyst versus pyogenic granuloma (n = 1), and lymphoma (n = 1). This work has been reported in line with the PROCESS criteria. DISCUSSION: The final histopathological diagnosis was unexpectedly invasive squamous cell carcinoma (SCC) in 4, one SCC in-situ, and squamous dysplasia in one. The primary treatment included MMC 0.02 % for 2 cycles for chemo-reduction in one of the cases where OSSN was suspected. Excisional biopsy was performed eventually for all lesions with application of one or more of the following modalities: MMC 0.02 %, absolute alcohol 99 %, and cryotherapy to the conjunctival margin. No tumor recurrence was noted in any of the patients after an average period of follow-up of 26 months. Even though the outcome was good, tumor-related morbidity and delay in the referral by general ophthalmologists are to be considered. CONCLUSION: Conjunctival OSSN has wide presentation clinically and can be challenging in terms of diagnosis. Histopathological evaluation is essential for a definitive diagnosis and treatment. Accurate clinical diagnosis might affect the management plan with consideration for topical therapeutic modalities, however, these cases are best managed by wide excision using the no-touch technique and double-freeze-thaw cryotherapy to the conjunctiva with consideration of topical chemotherapy.

A case of ciliary body mesectodermal leiomyoma with rapid growth and loss of vision necessitating enucleation.

INTRODUCTION: Mesectodermal leiomyoma of the ciliary body is a benign rare tumor that rarely presents acutely with a complicated clinical course. PRESENTATION OF CASE: We are reporting a 39-year-old healthy female who presented with subacute blurred vision in her right eye secondary to a ciliary body mass. Initial fine needle aspiration biopsy ruled out a melanoma but the patient meanwhile experienced rapid complicated growth of the mass with vision loss, for which her right globe was eventually enucleated. The tumor was diagnosed histopathologically to be mesectodermal leiomyoma. DISCUSSION: The clinical course of our case was unique because of the subacute onset of her symptoms, the rapid growth of her benign tumor, and the complicated tumor behaviour leading to enucleation. An acute presentation of mesectodermal leiomyoma has been reported only once among similar cases in the recent literature. The tumor in our case showed the characteristic histopathological and immunohistochemical findings described before. CONCLUSION: Ophthalmologists should be aware of the unusual acute/subacute presentation of a rather benign lesion. Delayed diagnosis may result in ophthalmic complications and loss of the globe.

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.

Photodynamic Therapy for Circumscribed Choroidal Hemangioma in 79 Consecutive Patients: Comparative Analysis of Factors Predictive of Visual Outcome.

PURPOSE: To determine factors predictive of visual outcome in patients with circumscribed choroidal hemangioma treated with photodynamic therapy (PDT). DESIGN: Retrospective case series. PARTICIPANTS: Seventy-nine patients with circumscribed choroidal hemangioma treated with PDT. METHODS: Patients with circumscribed choroidal hemangioma treated with PDT were identified, and factors predictive of final visual acuity were assessed. MAIN OUTCOME MEASURES: Factors predictive of final visual acuity of 20/40 or better versus 20/50 or worse. RESULTS: Seventy-nine eyes of 79 patients with circumscribed choroidal hemangioma were treated with PDT. All tumors were unilateral and posterior to the equator. Mean largest basal diameter was 5.7 mm (range, 2.0-10.0 mm); mean thickness was 3.0 mm (range, 1.4-4.5 mm). A total of 116 PDT sessions were performed (mean, 1.5 sessions; range, 1.0-7.0 sessions). Standard duration PDT was used in most cases (83 seconds; n = 110/116 [95%]). Mean follow-up was 43 months. Of 79 patients, 49 (62%) demonstrated good visual acuity (≥20/40) and 30 (38%) showed intermediate to poor visual acuity (≤20/50) after PDT. A comparison (final visual acuity, good vs. intermediate to poor) revealed a statistically significant difference in baseline features of photopsia (100% vs. 0%; P = 0.04), initial visual acuity of 20/40 or better (77% vs. 23%; P < 0.001), mean tumor basal diameter (5.4 mm vs. 6.2 mm; P = 0.03), mean tumor thickness (2.9 mm vs. 3.2 mm; P = 0.01), cystoid macular edema (CME) involving the foveola (30% vs. 70%; P = 0.001), retinal edema overlying the lesion (39% vs. 61%; P = 0.003), retinoschisis involving the foveola (0% vs. 100%; P = 0.002), lack of CME regardless of foveola involvement at presentation (79% vs. 21%; P < 0.001), previous treatment (33% vs. 67%; P = 0.04), and CME progression after treatment (0% vs. 100%; P = 0.006). Partial or complete resolution of subretinal fluid was achieved in 93% of patients. CONCLUSIONS: In this comparative analysis, PDT was an effective treatment method for circumscribed choroidal hemangioma. Good final visual outcome (≥20/40) was correlated with good baseline visual acuity, smaller tumor size, lack of CME, and lack of treatment before PDT.

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs.

Atypical posterior scleritis mimicking choroidal melanoma.

We report a case of atypical posterior scleritis mimicking amelanotic choroidal melanoma. A 30-year-old healthy Filipino man, with a history of painless subacute loss of vision in his left eye over 5 months, was referred to our institute for further workup and management. On examination, visual acuity of the left eye was 20/200. Anterior segment examination yielded unremarkable results, with injected conjunctiva and quiet episcleral blood vessels, while fundus examination revealed non-pigmented nasal choroidal mass, with significant subretinal fluid resembling amelanotic choroidal melanoma. Right eye examination yielded unremarkable results. The patient was diagnosed with atypical posterior scleritis, and treated with oral steroids for 2 weeks, with no improvement. A periocular steroid was then injected to the left eye, causing dramatic reduction in choroidal mass size, and complete resolution of subretinal fluid. The visual acuity improved to 20/28.5 one month after the injection. Timely treatment was crucial for minimizing vision-threatening complications.

Indications for enucleation and evisceration in a tertiary eye hospital in Riyadh over a 10-year period.

BACKGROUND: Enucleation and evisceration are eye removal procedures considered as palliative treatment when all other therapeutic options are exhausted. OBJECTIVE: Describe the causes and histopathological findings leading to enucleation/evisceration, and correlate the clinical findings with the histopathological findings. DESIGN: Retrospective, descriptive study. SETTINGS: Tertiary care hospital, Riyadh, Saudi Arabia. PATIENTS AND METHODS: The medical records of patients who underwent enucleation or evisceration from February 2005 to May 2015 were reviewed. Patients were classified into two categories based on indications of surgery: traumatic and nontraumatic. Causes of ocular injury in the traumatic group were documented, and the histopathological findings were reviewed for the nontraumatic cases. MAIN OUTCOME MEASURE(S): Number of enucleation and evisceration surgeries and their causes and histopathological findings. RESULTS: One hundred ten patients underwent evisceration (n=69, 63%) and enucleation (n=41, 37%). Causes were traumatic in 38 (35%) and nontraumatic in 72 (65%). The median age was 50 years and there were 64 men and 46 women. Postoperative endophthalmitis was the most common indication for surgery (n=24, 21.8%), followed by painful blind eye (n=22, 20%). Ocular trauma was more predominant in men (n=29, 76%) than in women (n=9, 24%), and the leading mechanism of trauma was metallic nail injuries (n=6, 15.8%). In the nontraumatic group, endophthalmitis was the most common histopathological finding (n=25, 34.7%). CONCLUSIONS: The majority of the eye enucleation/evisceration surgeries were due to nontraumatic causes, especially postoperative infections. However, severe eye trauma was still a main indication for this destructive procedure. Guidelines are needed to decrease the incidence/severity of work-related eye injuries and to detect and manage eye infections earlier and more promptly. LIMITATIONS: Retrospective study, in one hospital in one area; therefore, results cannot be generalized.

Predictors of performance in an ophthalmology residency program.

OBJECTIVE: To assess the value of current selection criteria and additional factors as predictors of performance in an ophthalmology residency training program. DESIGN: A retrospective study. PARTICIPANTS: Data were collected from the files of 166 residents who were collectively trained in an ophthalmology residency program from 2000 to 2013. METHODS: The program's selection criteria included medical school grade point average (GPA), Saudi licensing examination (SLE) score, multiple-choice question ophthalmology selection (MCQ) examination score, and interview mark. Indicators of performance included average scores in the promotion examination for 4 years of training (average R), King Saud University fellowship examination (KSU) score, and Saudi Board in Ophthalmology examination (SBO) score. An average of KSU and SBO scores was also used as a performance indicator. Times of program completion and average performance score across all years in the residency program were used as second-level indicators of performance. RESULTS: There were strong correlations between the MCQ examination score and each training performance indicator (average R, KSU score, SBO score, and average of KSU and SBO scores; p = 0.002, 0.008, 0.05, and 0.002, respectively). The interview mark correlated well with average R (p = 0.001) but not with other indicators. The MCQ examination score and the interview mark were the only predictors of second-level indicators of performance (p = 0.009 and 0.029, respectively). CONCLUSIONS: The MCQ examination score and interview mark were the 2 best predictors of performance as an ophthalmology resident. GPA and SLE score were poor predictors of performance.

Exome-based case-control association study using extreme phenotype design reveals novel candidates with protective effect in diabetic retinopathy.

UNLABELLED: Diabetic retinopathy (DR) is a common clinical expression of diabetes mellitus-induced vasculopathy and is a major cause of vision loss. Significant gaps remain in our understanding of the molecular pathoetiology of DR, and it is hoped that human genetic approaches can reveal novel targets especially since DR is a heritable trait. Previous studies have focused on genetic risk factors of DR but their results have been mixed. In this study, we hypothesized that the use of the extreme phenotype design will increase the power of a genomewide search for "protective" genetic variants. We enrolled a small yet atypical cohort of 43 diabetics who did not develop DR a decade or more after diagnosis (cases), and 64 diabetics with DR (controls), all of similar ethnic background (Saudi). Whole-exome sequencing of the entire cohort was followed by statistical analysis employing combined multivariate and collapsing methods at the gene level, to identify genes that are enriched for rare variants in cases vs. CONTROLS: Three genes (NME3, LOC728699, and FASTK) reached gene-based genome-wide significance at the 10(-08) threshold (p value = 1.55 × 10(-10), 6.23 × 10(-10), 3.21 × 10(-08), respectively). Our results reveal novel candidate genes whose increased rare variant burden appears to protect against DR, thus highlighting them as attractive candidate targets, if replicated by future studies, for the treatment and prevention of DR. Extreme phenotype design when implemented in sequencing-based genome-wide case-control studies has the potential to reveal novel candidates with a smaller cohort size compared to standard study designs.

Is systemic infliximab therapy effective for retinal cavernous hemangioma?

A 10-month-old infant with the diagnosis of retinal cavernous hemangioma involving the macula presented with an outward deviation of the right eye that has been noticed by her parents. Examination revealed a clearing vitreous hemorrhage, and grape-like clusters filled with blood in the posterior pole. After 4 cycles of intravenous infliximab over the period of 3 months, no evident change was noted on the size of the cavernous hemangioma. 

Bilateral lacrimal gland disease: clinical features of 97 cases.

OBJECTIVE: Bilateral lacrimal gland (LG) disease is a unique presentation that can result from varied causes. We reviewed the diagnoses, clinical features, and outcomes of 97 patients with this entity. DESIGN: Case series. PARTICIPANTS: Ninety-seven patients with bilateral LG disease. METHODS: Retrospective review and statistical analysis using analysis of variance and the Fisher exact test. MAIN OUTCOME MEASURES: Patient demographics, clinical features, diagnostic testing, diagnosis, and treatment. RESULTS: Patient age ranging from 8 to 84 years (mean, 46 years). The predominant gender was female (77%), and race included black (49%), white (38%), and Hispanic (12%) patients. Diagnoses fell into 4 categories: inflammatory (n = 51; 53%), structural (n = 20; 21%), lymphoproliferative (n = 19; 20%), and uncommon (n = 7; 7%) entities. The most common diagnoses included idiopathic orbital inflammation (IOI; n = 29; 30%), sarcoidosis (n = 19; 20%), prolapsed LG (n = 15; 15%), lymphoma (n = 11; 11%), lymphoid hyperplasia (n = 8; 8%), and dacryops (n = 5; 5%). Inflammatory conditions were more likely in younger patients (P<0.05) and in those with pain (P<0.001) and mechanical blepharoptosis (P<0.01) at presentation, whereas lymphoma was more common in older patients (P<0.001) without active signs of inflammation at presentation. Black patients were more likely to have sarcoidosis (P<0.01). Laboratory results showed high angiotensin converting enzyme level being significantly more likely in patients with sarcoidosis (P<0.05). However, sensitivity was limited to 45%, with 25% of patients diagnosed with IOI also demonstrating positive results. Corticosteroid therapy was the treatment of choice in 38 cases, corresponding to resolution of symptoms in 29% and improvement in an additional 32%. Overall, chronic underlying disease was found in 71% of patients, among whom 26% achieved a disease-free state, whereas 3% succumbed to their underlying disease. CONCLUSIONS: The cause of bilateral lacrimal gland disease most commonly was inflammatory, followed by structural and lymphoproliferative. Patient characteristics and clinical presentations were key features distinguishing between competing possibilities. Despite local control with corticosteroids or radiotherapy, underlying disease continued in 71% of patients and led to death in 3%.

Enhanced depth imaging optical coherence tomography of choroidal metastasis in 14 eyes.

PURPOSE: To describe the imaging features of choroidal metastasis using enhanced depth imaging optical coherence tomography (EDI-OCT). METHODS: This retrospective observational case series included 31 eyes with choroidal metastasis. Spectral domain EDI-OCT was performed using Heidelberg Spectralis HRA + OCT. The main outcome measures were imaging features by EDI-OCT. RESULTS: Of 31 eyes with choroidal metastasis imaged with EDI-OCT, 14 (45%) eyes displayed image detail suitable for study. The metastasis originated from carcinoma of the breast (n = 7, 50%), lung (n = 5, 36%), pancreas (n = 1, 7%), and thyroid gland (n = 1, 7%). The mean tumor basal diameter was 6.4 mm, and mean thickness was 2.3 mm by B-scan ultrasonography. The tumor location was submacular in 6 (43%) eyes and extramacular in 8 (57%) eyes. By EDI-OCT, the mean tumor thickness was 987 µm. The most salient EDI-OCT features of the metastasis included anterior compression/obliteration of the overlying choriocapillaris (n = 13, 93%), an irregular (lumpy bumpy) anterior contour (n = 9, 64%), and posterior shadowing (n = 12, 86%). Overlying retinal pigment epithelial abnormalities were noted (n = 11, 78%). Outer retinal features included structural loss of the interdigitation of the cone outer segment tips (n = 9, 64%), the ellipsoid portion of photoreceptors (n = 8, 57%), external limiting membrane (n = 4, 29%), outer nuclear layer (n = 1, 7%), and outer plexiform layer (n = 1, 7%). The inner retinal layers (inner nuclear layer to nerve fiber layer) were normal. Subretinal fluid (n = 11, 79%), subretinal lipofuscin pigment (n = 1, 7%), and intraretinal edema (n = 2, 14%) were identified. CONCLUSION: The EDI-OCT of choroidal metastasis shows a characteristic lumpy bumpy anterior tumor surface and outer retinal layer disruption with preservation of inner retinal layers.

Monthly intravitreal bevacizumab for macular edema after iodine-125 plaque radiotherapy of uveal melanoma.

PURPOSE: To examine the efficacy of monthly injections of intravitreal bevacizumab (IVB) for macular edema after iodine-125 plaque radiotherapy of uveal melanoma. METHODS: We studied 36 patients with macular edema after plaque radiotherapy of uveal melanoma in this noncomparative, interventional case series. All eyes were treated with 4 monthly injections of IVB. Central macular thickness (CMT) and best-corrected visual acuity (BCVA) were measured before each injection and 4-6 months after the first injection. The main outcome measures were change in CMT and BCVA. RESULTS: At 4-6 months following the first IVB, 20 eyes (56%) had decreased CMT, 11 eyes (31%) had stable CMT, and 5 eyes (14%) had increased CMT. The mean change in CMT and the mean percent change in CMT at 4-6 months compared to baseline were -91 µm (-20%) in all eyes, -174 µm (-37%) in the group with decreased macular thickness, -14 µm (-3%) in the group with stable macular thickness, and +69 µm (+17%) in the group with increased macular thickness. At 4-6 months, 15 eyes (42%) had increased BCVA, 16 eyes (44%) had stable BCVA, and 5 eyes (14%) had decreased BCVA. An increase in CMT was seen between the fourth monthly IVB injection and the final evaluation at 4-6 months after the first injection in all 3 groups of our study. CONCLUSIONS: At 4-6 months following the first injection, 4 monthly injections of IVB in eyes with macular edema after plaque radiotherapy of uveal melanoma decreased macular edema in 56% and improved BCVA in 42% of the treated eyes.

Intravitreal bevacizumab at 4-month intervals for prevention of macular edema after plaque radiotherapy of uveal melanoma.

PURPOSE: To evaluate the efficacy of intravitreal bevacizumab for prevention of macular edema after plaque radiotherapy of uveal melanoma. DESIGN: Retrospective, single-center, nonrandomized, interventional comparative study. PARTICIPANTS: Patients with uveal melanoma treated with plaque radiotherapy were divided into 2 groups: a bevacizumab group and a control group. INTERVENTION: The bevacizumab group received intravitreal bevacizumab injection at the time of plaque removal and every 4 months thereafter for 2 years (total, 7 injections). The control group had no intravitreal bevacizumab injection. Both groups had periodic follow-up with ophthalmoscopy and optical coherence tomography (OCT). MAIN OUTCOME MEASURES: Development of OCT-evident macular edema. RESULTS: There were 292 patients in the bevacizumab group and 126 in the control group. The median foveolar radiation dose was 4292 cGy (bevacizumab) and 4038 cGy (control; P = 0.327). The cumulative incidence of OCT-evident macular edema over 2 years (bevacizumab group vs. control group) was 26% versus 40% (P = 0.004), respectively; that for clinically evident radiation maculopathy was 16% versus 31% (P = 0.001), respectively; that for moderate vision loss was 33% versus 57% (P < 0.001), respectively; and that for poor visual acuity was 15% versus 28% (P = 0.004), respectively. There was no statistically significant difference in clinically evident radiation papillopathy (P = 0.422). Kaplan-Meier estimates at 2 years showed statistically significantly reduced rates of OCT-evident macular edema (P = 0.045) and clinically evident radiation maculopathy (P = 0.040) in the bevacizumab group compared with controls. CONCLUSIONS: Patients receiving intravitreal bevacizumab injection every 4 months after plaque radiotherapy for uveal melanoma demonstrated OCT-evident macular edema, clinically evident radiation maculopathy, moderate vision loss, and poor visual acuity less frequently over a period of 2 years than patients not receiving the injections.

Management of advanced retinoblastoma with intravenous chemotherapy then intra-arterial chemotherapy as alternative to enucleation.

PURPOSE: To determine the efficacy of primary intravenous chemotherapy (IVC) plus secondary intraarterial chemotherapy (IAC) for patients with advanced retinoblastoma. METHODS: Retrospective, nonrandomized interventional case series of 14 patients with retinoblastoma managed with primary systemic IVC (vincristine, etoposide, and carboplatin for 6 cycles) followed by secondary IAC (melphalan for 1-6 cycles). RESULTS: Fourteen patients with advanced retinoblastoma classified by the International Classification of Retinoblastoma as Group D (n = 6, 43%) or Group E (n = 8, 57%) were treated with IVC as primary treatment and subsequent secondary IAC as rescue or consolidation therapy. The IAC was given for recurrent retinoblastoma and/or subretinal/vitreous seeds in 13 eyes (93%) and for persistent viable retinoblastoma in 1 eye (7%). Enucleation was the alternative option. The mean interval between IVC completion and IAC start was 40 weeks (median, 11 weeks; range, 2-170 weeks) and the mean number of IAC cycles was 3 (median, 3; range, 1-6). After primary IVC plus secondary IAC, globe salvage was achieved in 8 patients (57%) at mean 2-year follow-up. There was no evidence of retinoblastoma metastasis or death and no sign of second cancer or life-threatening complication. CONCLUSION: For advanced retinoblastoma (Groups D and E) in which enucleation is the alternative option, primary systemic IVC followed by secondary focal IAC provides globe salvage in 57% of the eyes and with no metastatic event.

Genomic profile of 320 uveal melanoma cases: chromosome 8p-loss and metastatic outcome.

PURPOSE: Uveal melanoma (UM) was a fatal malignancy in 40% to 50% of cases. The aim of this study is to evaluate the independent contributions of chromosome 1, 3, 6, and 8 abnormalities for prognostication of metastasis, and to define multichromosome copy number aberration (CNA) signatures that can be used to evaluate risk. METHODS: A series of 320 UM were analyzed for chromosome 1, 3, 6, and 8 abnormalities using whole genome single-nucleotide polymorphism arrays. Results for changes in six chromosomal regions were analyzed using univariate and multivariate Cox proportional hazard modeling to identify significant predictors of metastasis and CNA signatures. RESULTS: Univariate Cox analysis indicated that losses of chromosome 3, 1p, 6q, and 8p and gain of 8q, as well as sex, source of tumor tissue (fine-needle aspiration biopsy [FNAB] compared with tumor from an enucleated eye), tumor basal diameter and height, and ciliary body involvement were all significant predictors of poor metastatic outcome. In the multivariate analysis, loss of chromosome 3 and 8p remained significant after adjusting for the effects of all other variables, as did sex, tissue source, and basal diameter. Multivariate analysis of the joint effects of changes in the six chromosomal regions showed that six signatures, including chromosome 3-loss, 1p-loss, 8p-loss, and/or 8q-gain had hazard ratios (HR) ranging from 7.90 to 37.25. CONCLUSIONS: In UM, tumor size and location, tissue source, and sex were all significantly associated with increased metastasis. In addition, chromosome 3-loss and 8p-loss were found to be independent predictors of poor metastatic outcome and CNA signatures were identified that can add a specific HR value for classification of risk categories.

Retinal vasoproliferative tumors: comparative clinical features of primary vs secondary tumors in 334 cases.

OBJECTIVE: To compare the clinical features of primary vs secondary retinal vasoproliferative tumors (VPTs). METHODS: Retrospective case series of 334 tumors in 295 eyes of 275 patients. RESULTS: Of 275 patients with VPT, 41% (n = 113) were male and 59% (n = 162) were female, with a mean age of 44 years at presentation. Primary VPT occurred in 80% (n = 219) and secondary VPT, in 20% (n = 56) of patients. Secondary VPT (n = 67) occurred in eyes with retinitis pigmentosa (n = 15, 22%), pars planitis (n = 14, 21%), Coats disease (n = 11, 16%), previous retinal detachment surgery (n = 8, 12%), idiopathic peripheral retinal vasculitis (n = 4, 6%), familial exudative vitreoretinopathy (n = 3, 4%), and others (n = 12, 18%). The mean interval between diagnosis of underlying ocular condition and secondary VPT was 160 months. Statistically significant differences (P < .05) in clinical features (primary vs secondary VPTs) included mean age at presentation (46 vs 38 years), visual symptoms (74% vs 87%), poor visual acuity worse than 20/200 (15% vs 28%), bilaterality (4% vs 20%), multifocality (5% vs 15%), postequatorial tumor location (20% vs 33%), tumor basal dimension (6 vs 7 mm), anterior chamber cells (16% vs 30%), and vitreous cells (19% vs 48%). CONCLUSIONS: Retinal vasoproliferative tumor can be primary (80%) or secondary (20%). Compared with primary VPT, secondary VPT is more often bilateral, multiple, and larger and occurs at an earlier age associated with poorer visual acuity.

High-risk retinoblastoma based on international classification of retinoblastoma: analysis of 519 enucleated eyes.

PURPOSE: To determine the correlation between the International Classification of Retinoblastoma (ICRB) and histopathologic high-risk retinoblastoma. DESIGN: Retrospective study. PARTICIPANTS: A total of 519 patients. INTERVENTION: Primary enucleation. MAIN OUTCOME MEASURES: High-risk retinoblastoma, metastasis, and death. RESULTS: Of 519 primarily enucleated eyes, 87 (17%) were classified as group D and 432 (83%) were classified as group E on the basis of the ICRB. High-risk retinoblastoma was identified in 23% (117/519) of enucleated eyes, including 17% (15/87) group D and 24% (102/432) group E eyes. High-risk histopathologic features of retinoblastoma included anterior chamber involvement (5/15 [33%] group D eyes, 31/102 [30%] group E eyes), isolated massive posterior uveal invasion ≥ 3 mm (7/15 [47%] group D eyes, 22/102 [22%] group E eyes), isolated post-laminar optic nerve invasion (2/15 [13%] group D eyes, 46/102 [45%] group E eyes), and any combination of posterior uveal invasion and optic nerve involvement (7/15 [47%] group D eyes, 37/102 [36%] group E eyes). On logistic regression analysis, massive posterior uveal invasion ≥ 3 mm was more common in group D eyes (P = 0.0442), and post-laminar optic nerve invasion was more common in group E eyes (P = 0.0390). Of 117 patients with high-risk retinoblastoma, systemic adjuvant chemotherapy was administered in 83 patients (71%). Systemic metastasis developed in 0% (0/15) of those with high-risk group D retinoblastoma and 10% (10/102) of those with high-risk group E retinoblastoma over a mean follow-up period of 78 months (median, 62 months; range, 1-419 months). There was no metastasis in any patient (n = 402) classified with non-high-risk retinoblastoma. Of the 10 patients who developed metastasis, 4 had received prior adjuvant chemotherapy and 6 had no prior adjuvant chemotherapy. There was no metastasis in high-risk patients treated with vincristine sulphate, etoposide phosphate, and carboplatin (VEC). Death from metastasis occurred in 4% of high-risk patients (5/117). CONCLUSIONS: On the basis of the ICRB, 17% of group D and 24% of group E eyes are at increased risk for metastatic disease. In this study, 8% of patients developed metastasis. There was no metastasis in any patient classified with non-high-risk retinoblastoma. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Interferon for ocular surface squamous neoplasia in 81 cases: outcomes based on the American Joint Committee on Cancer classification.

PURPOSE: To assess the efficacy of interferon alpha-2b (IFNα2b) in the management of ocular surface squamous neoplasia (OSSN). METHODS: This is a retrospective, nonrandomized interventional case series study of 80 patients with 81 tumors treated with IFNα2b eye drops and/or injection combined with surgical excision when necessary. The main outcome measure was complete response or partial response based on the American Joint Committee on Cancer classification. RESULTS: The OSSN was classified as Tis (n = 10, 12%), T1 (n = 13, 16%), T2 (n = 6, 7%), T3 (n = 51, 63%), and T4 (n = 1, 1%). IFNα2b was used as immunotherapy alone (n = 22, 27%) or combined with surgery (n = 59, 73%). Overall (n = 81), complete response was achieved in 90% Tis, in 100% T1, in 100% T2, in 94% T3, and in 100% T4. Specifically for immunotherapy (n = 22), IFNα2b alone achieved complete response in 75% (3/4) Tis, in 100% (8/8) T1, and in 70% (7/10) T3. Planned IFNα2b plus surgery (n = 59) achieved control in 100% (6/6) Tis, in 100% (5/5) T1, in 100% (6/6) T2, in 100% (41/41) T3, and in 100% (1/1) T4. Tumor recurrence was noted in 5% (4/81) of cases over a median follow-up of 1 year. Ocular side effects included conjunctival hyperemia (n = 4, 5%), ocular irritation (n = 3, 4%), superficial punctate keratitis (n = 3, 4%), and conjunctival follicles (n = 1, 1%). Systemic side effects included postinjection flu-like syndrome for 1 day (n = 7, 9%). CONCLUSIONS: IFNα2b, when appropriately combined with surgical excision for OSSN, provides complete control in 95% of cases overall, specifically in 90% Tis, in 100% T1, in 100% T2, in 94% T3, and in 100% T4.

American Joint Committee on Cancer (AJCC) clinical classification predicts conjunctival melanoma outcomes.

PURPOSE: The aim of this study was to evaluate conjunctival melanoma outcomes based on American Joint Committee on Cancer classification. The study design constituted a nonrandomized interventional case series. METHODS: This was a retrospective chart review comprising 343 participants, and the main outcome measures were melanoma local recurrence, lymph node metastasis, distant metastasis, and death. RESULTS: On the basis of the American Joint Committee on Cancer classification (seventh edition), conjunctival melanoma was classified as T1 (196 [57%]), T2 (110 [32%]), T3 (37 [11%]), and T4 (0). The mean tumor basal diameter increased with tumor staging with 8.5 mm for T1, 12.7 mm for T2 (p = 0.0003), and 16 mm for T3 (p < 0.0001). The melanoma arose from primary acquired melanosis (T1 = 71%; T2 = 84%; T3 = 81%), preexisting nevus (T1 = 8%; T2 = 5%; T3 = 3%), or de novo (T1 = 21%; T2 = 12%; T3 = 16%). Outcomes at 5 years (Kaplan-Meier) revealed melanoma local recurrence/new tumor in 44% T1, 78% T2 (p < 0.0001), and 76% T3 (P=0.0044); regional lymph node metastasis in 17% T1, 52% T2 (p < 0.0001), and 49% T3 (p = 0.0092); melanoma-related distant metastasis in 11% T1, 35% T2 (p < 0.0001), and 42% T3 (p = 0.0018); and melanoma-related death in 5% T1, 20% T2 (p = 0.0655), and 23% T3 (p = 0.0526). Based on American Joint Committee on Cancer classification, factors predictive of melanoma recurrence included T2 stage (p < 0.0001), and T3 stage (p = 0.0061). After adjusting for tumor origin, factors predictive of regional lymph node metastasis, melanoma-related distant metastasis, and melanoma-related death included melanoma arising de novo (p < 0.0001; p < 0.0001; p < 0.0001), T2 stage (p < 0.0001; p < 0.0001; p = 0.007), and T3 stage (p = 0.005; p = 0.0014; p = 0.0342). CONCLUSION: The American Joint Committee on Cancer staging predicts prognosis of conjunctival melanoma. Melanoma classified as T2 and T3 (compared with T1) showed significantly higher rates of local recurrence, regional lymph node metastasis, distant metastasis, and death.