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.

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.

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.

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.

Photodynamic therapy for choroidal metastasis in 8 cases.

PURPOSE: To determine the efficacy of photodynamic therapy (PDT) in the treatment of choroidal metastasis. DESIGN: Retrospective, interventional case series. PARTICIPANTS: Nine tumors in 8 eyes of 8 patients. INTERVENTION: Photodynamic therapy using verteporfin at a dose of 6 mg/m(2) body surface area and 689 nm diode laser at an intensity of 600 mW/cm(2) for 83 seconds (50 J/cm(2)). MAIN OUTCOME MEASURES: Tumor control and best-corrected visual acuity. RESULTS: Nine choroidal metastases in 8 eyes were treated with 1 (8 tumors) or 2 (1 tumor) sessions of PDT. The mean tumor basal diameter was 7 mm (median, 7 mm [range, 2-13 mm]), and mean tumor thickness was 2.9 mm (median, 2.9 mm [range, 1.6-4 mm]). All 9 tumors were associated with shallow subretinal fluid. After PDT, complete control with resolution of subretinal fluid was achieved in 7 tumors (78%), with mean tumor thickness reduction of 39% (median, 43% [range, 6%-61%]). Two tumors failed to respond to PDT, both requiring plaque radiotherapy. Improvement or stabilization of vision was achieved in 7 eyes. Photodynamic therapy-related complications included intraretinal hemorrhage in 1 eye. CONCLUSIONS: Photodynamic therapy can be an effective alternative for the treatment of choroidal metastasis. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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.

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.

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.

Incidence, Risk Factors and Surgical Outcomes of Cataract among Patients with Uveitis in a University Referral Hospital in Riyadh, Saudi Arabia.

Purpose: To investigate incidence, risk factors, and surgical outcomes of cataract among uveitis patients. Methods: Retrospective review of 1000 patients (1582 eyes). Results: At initial presentation, cataract was diagnosed in 290 (18.3%) eyes and was most common in eyes with anterior uveitis. Fuchs' uveitis, herpetic uveitis, and presumed tuberculous uveitis were leading clinical entities associated with cataract at presentation. During follow-up, cataract developed in additional 200 (12.6%) eyes and was most common in eyes with anterior uveitis. Significant risk factors at presentation included age >18 years, female gender, presence of keratic precipitates, hypopyon, and posterior synechiae. Among the 490 eyes with cataract, 204 underwent cataract extraction during follow-up period. Best corrected vision of ≥20/40 was achieved in 122 (60.1%) eyes. Conclusions: Incidence of cataract differed depending on anatomic and etiologic diagnoses of uveitis. There is a significant association between severity of inflammation at presentation and development of cataract.

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.

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. 

Acute exudative paraneoplastic polymorphous vitelliform maculopathy in five cases.

BACKGROUND AND OBJECTIVE: To evaluate clinical features, course, and outcome of patients with acute exudative paraneoplastic polymorphous vitelliform maculopathy (AEPPVM). PATIENTS AND METHODS: Retrospective case series of 5 patients. RESULTS: There were 3 males and 2 females, with a median age of 74 years. The primary neoplasms were cutaneous melanoma (n = 2), choroidal melanoma (n = 1), lung adenocarcinoma (n = 1), and lung plus breast adenocarcinoma (n = 1). The mean interval between the diagnosis of the primary neoplasm and the diagnosis of AEPPVM was 42 months. The presenting symptom was blurred vision in all cases. Ophthalmoscopy disclosed multifocal localized shallow serous detachments of the post-equatorial neurosensory retina with yellow-white subretinal debris confirmed by optical coherence tomography (OCT). There was a mean of 21 individual sites of detachment per eye, each measuring a mean of approximately 0.8 millimeter in diameter. Fundus autofluorescence depicted hyperautofluorescence corresponding to the detachments. After mean follow-up of 5 months, three patients had died of metastases. Of the two survivors, one showed resolution of lesions and the other was unchanged. CONCLUSION: AEPPVM is a paraneoplastic retinopathy found in patients with metastatic melanoma or carcinoma. The most salient feature is reduced visual acuity from multifocal shallow retinal detachments less than 1-mm diameter, best depicted on OCT.