Characteristics of patients with recurrent retinoblastoma: a survival analysis.

BACKGROUND: Management guidelines and corresponding survival data for patients with recurrent retinoblastoma (RB) are lacking. This study aimed to summarize the clinical characteristics of patients with recurrent RB and analyze their survival outcomes. METHODS: We retrospectively analyzed 68 patients with recurrent RB who underwent treatment in our institution from January 2016 to December 2020. Patients were grouped according to location of recurrence: intraocular, orbital, and distant metastasis. RESULTS: The male:female ratio was 1.3:1 and the median age at recurrence was 37.5 months (range, 30.3-62.8). The number of patients in the intraocular recurrence, orbital recurrence, and metastasis groups was 13 (19.1%), 23 (33.8%), and 32 (47.1%), respectively. Thirty patients died, 36 were alive at last follow-up, and two were lost to follow-up. Eye enucleation was performed in 94.1% of patients. Five-year overall survival in patients with intraocular recurrence, orbital recurrence, and metastasis was 84.6%, 69.6%, and 31.3%, respectively (P = 0.001). Most deaths occurred within 2 years of recurrence. Presence of high-risk pathological factors, central nervous system invasion, and absence of combination therapy were independent predictors of worse 5-year overall survival. CONCLUSION: The rate of eye preservation in survivors of recurrent RB was very low. Although 5-year overall survival in patients who underwent treatment for intraocular and orbital recurrence was high, it was low in those with metastasis. RB patients may need lifelong follow-up for recurrence and secondary malignancy.

SILICONE FINE-NEEDLE ASPIRATION RETINAL BIOPSY: A Novel Surgical Technique for Vitreoretinal Lymphoma.

PURPOSE: To describe a 41-gauge silicone fine-needle aspiration biopsy (S-FNAB) technique and assess its value in diagnosing primary vitreoretinal lymphoma (PVRL). METHODS: Retrospective review of seven consecutive patients who underwent vitreous biopsy (VB) and 41-gauge S-FNAB of retinal/subretinal lesions in a single tertiary center between January 2012 and March 2023. RESULTS: Of seven patients, S-FNAB confirmed the diagnosis of PVRL in six patients. In five of those patients, both VB and retinal/subretinal S-FNAB (performed at the same procedure) yielded positive results, with the retinal thickness at the biopsy site as small as 231 µm. Four of these five patients had one or more previous negative VB. In one patient, S-FNAB yielded positive results despite a negative VB. Silicone fine-needle aspiration biopsy failed to confirm positive VB for PVRL in the remaining patient. The time from symptom onset to diagnosis of PVRL ranged from 18 days to 26 months. There were no severe complications associated with the procedure. CONCLUSION: Silicone fine-needle aspiration biopsy might be a valuable method for obtaining a sufficient sample of viable cells to diagnose PVRL. It can be performed as a primary procedure along with VB. Further studies are warranted to determine where this technique could be most advantageous.

Clinical characterization and long-term postoperative outcomes of retinoblastoma patients receiving enucleation and primary orbital implantation in early infancy: an observational study.

OBJECTIVES: To retrospectively investigate clinical characterization and the long-term postoperative outcomes of retinoblastoma (RB) patients receiving enucleation with primary orbital implantation in early infancy (0-6 months old). METHODS: The clinical and follow-up data of 42 RB patients receiving enucleation with primary orbital implantation in early infancy at Beijing Tongren Hospital from December 2009 to January 2020 were analysed. The average follow-up time was 83 months. The patient group included 24 males and 18 females, 30 unilateral and 12 bilateral cases. A total of 44 eyes with 10 in stage D and 34 in stage E underwent 40 unilateral and 2 bilateral surgeries. 17 RB eyes received hydrogel and 27 RB eyes received hydroxyapatite implants. This study was performed by following the guideline of STROBE. RESULTS: Enucleation combined with primary orbital implantation promoted survival and was safe with few and minor complications such as increased secretion, upper eyelid ptosis, and sunken eye sockets which were not affected by stages, lateralities, or implant materials. 55-80% RB patients exhibited satisfactory appearance and obvious or moderate motility of orbital implants according to the evaluation by doctors and family members. Family members were likely more optimistic about the appearance and more pessimistic about motility of the orbital implantation than doctors did.The quality of life was high as indicated by PedsQL3.0 or PedsQL4.0 scores ( ≧ 90 for > 75% patients). It was not affected by the stages, laterality, and implant materials, nor affected by the appearance and motility of the implants. CONCLUSIONS: The outcomes of the combination of enucleation and primary orbital implantation for pertinent RB patients in early infancy are generally satisfactory with few and minor complications, high safety, appearance, and overall quality of life. Enucleation combined with primary orbital implantation in early infancy benefits pertinent RB patients in appearance, survival, and quality of life.

A retrospective study on adjuvant chemotherapy in retinoblastoma: validation of the new recommendation against treatment for pT2a tumors based on the 8th AJCC classification.

BACKGROUND: Retinoblastoma (RB) is an intraocular malignant tumor detected in early childhood with variable global impact. Histopathological classification of the tumor in enucleated globes with RB is the key for the decision of adjuvant chemotherapy use. We aim to validate the use of adjuvant chemotherapy in cases with combined pre-laminar/intralaminar optic nerve (ON) invasion and focal choroidal invasion according to the American Joint Committee on Cancer (AJCC) 8th classification. METHODS: This is a retrospective study conducted at King Abdulaziz University Hospital (KAUH) and King Khalid Eye Specialist Hospital (KKESH) in Riyadh, Saudi Arabia of all RB cases who underwent enucleation over 22 years (2000 to 2021). The histopathological findings were reviewed to identify the enucleated globes classified as pT2a tumors, as an inclusion criterion. Basic demographic and clinical data were collected via chart review Simple descriptive and basic statistical analysis of the data was used where applicable. RESULTS: Thirty-one patients who had an enucleated globe with RB that fit into the above classification were included. Sixteen were males and 15 were females. The median age was 14 months (IQR = 14 months). Most of the patients (93.5%) had no family history of RB. The commonest presentation was leukocoria in 87.1% followed by squint in 32.3%. Fourteen patients (45.2%) were treated by enucleation alone while 17 patients (54.8%) received adjuvant chemotherapy. Out of these, 7 patients had unilateral RB and the remaining 10 patients had bilateral RB. None of our patients developed recurrence or metastatic disease irrespective of the indication for adjuvant chemotherapy use after a maximum period of follow up reaching 17.84 years and a median of 10.6 years (IQR = 5.92). CONCLUSIONS: In patients with 8th AJCC histopathological classification of pT2a, chemotherapy following enucleation might not be justified. The outcome in our untreated group of patients did not differ from the treated group with the absence of metastasis after a relatively long period of follow up with a median exceeding 10 years in both groups. Therefore, the risk and benefit of post enucleation adjuvant chemotherapy in the treatment of unilateral RB should be carefully decided and discussed with the primary caregivers taking into consideration the most recent evidence and recommendations in the literature.

Strabismus management in retinoblastoma survivors.

PURPOSE: To report the result of strabismus surgery in eye-salvaged retinoblastoma (Rb) patients. METHODS: A retrospective case series including 18 patients with Rb and strabismus who underwent strabismus surgery after completing tumor treatment by a single pediatric ophthalmologist. RESULTS: A total of 18 patients (10 females and 8 males) were included with a mean age of 13.3 ± 3.0 (range, 2-39) months at the time tumor presentation and 6.0 ± 1.5 (range, 4-9) years at the time of strabismus surgery. Ten (56%) patients had unilateral and 8(44%) had bilateral involvement and the most common worse eye tumor's group was D (n = 11), C (n = 4), B (n = 2) and E (n = 1). Macula was involved by the tumors in 12 (67%) patients. The tumors were managed by intravenous chemotherapy (n = 8, 47%), intra-arterial chemotherapy (n = 7, 41%) and both (n = 3, 17%). After complete treatment, the average time to strabismus surgery was 29.9 ± 20.5 (range, 12-84) months. Except for one, visual acuity was equal or less than 1.0 logMAR (≤ 20/200) in the affected eye. Seven (39%) patients had exotropia, 11(61%) had esotropia (P = 0.346) and vertical deviation was found in 8 (48%) cases. The angle of deviation was 42.0 ± 10.4 (range, 30-60) prism diopter (PD) for esotropic and 35.7 ± 7.9 (range, 25-50) PD for exotropic patients (P = 0.32) that after surgery significantly decreased to 8.5 ± 5.3 PD in esotropic cases and 5.9 ± 6.7 PD in exotropic cases (P < 0.001). The mean follow-up after surgery was 15.2 ± 2.0 (range, 10-24) months, in which, 3 (17%) patients needed a second surgery. CONCLUSION: Strabismus surgery in treated Rb is safe and results of the surgeries are acceptable and close to the general population. There was not associated with tumor recurrence or metastasis.

Rehabilitation of pediatric retinoblastoma patients with ocular prostheses and their subsequent modifications: A 15-year retrospective study.

PURPOSE: Enucleation is a common treatment modality performed for pediatric retinoblastoma patients, and the resultant defects are reconstructed using an ocular prosthesis. The prostheses are modified or replaced periodically, as the child develops due to orbital growth and patient-error. The purpose of this report is to evaluate the replacement frequency of prostheses in the pediatric oncologic population. METHODS: A retrospective review was completed by the two senior research investigators, of patients that had ocular prostheses fabricated following enucleation of their retinoblastoma from 2005 to 2019 (n = 90). Data collected from the medical records of the patient included the pathology, date of surgery, date of prosthesis delivery, and the replacement schedule of the ocular prosthesis. RESULTS: During the 15-year study period, 78 enucleated observations (ocular prosthesis fabricated) were included for analysis. The median age of the patients at the time of delivery of their first ocular prosthesis was calculated to be 2.6 years (range 0.3-18 years). The median time to the first modification of the prosthesis was calculated to be 6 months. The time to modification of the ocular prosthesis was further stratified by age. CONCLUSION: Pediatric patients require modification of their ocular prostheses throughout their growth and development period. Ocular prostheses are reliable prostheses with predictable outcomes. This data is helpful to set an expectation among the patient, parent, and provider.

Diffusion-Weighted MR Imaging of the Optic Nerve Can Improve the Detection of Post-Laminar Optic Nerve Invasion from Retinoblastoma.

BACKGROUND: Post-laminar optic nerve invasion (PLONI) is a high-risk factor for the metastasis of retinoblastoma (RB). Unlike conventional MRI, diffusion-weighted imaging (DWI) reflects histopathological features, and may aid the assessment of PLONI. PURPOSE: To determine the value of conventional MRI plus DWI in detecting PLONI in RB patients. STUDY TYPE: Retrospective. POPULATION: Eighty-three RB patients, including 28 with histopathologically proven PLONI and 55 without PLONI. FIELD STRENGTH/SEQUENCE: 3.0 T, precontrast axial T1-weighted and T2-weighted imaging, DWI, and postcontrast axial, coronal, and oblique-sagittal T1-weighted imaging. ASSESSMENT: PLONI was assessed using post-enucleation histology and preoperative MRI features (optic nerve signal intensity, enlargement, and enhancement on conventional MRI, and apparent diffusion coefficient [ADC] of the optic nerve on DWI) evaluated by three observers. STATISTICAL TESTS: MRI features suggesting the presence of PLONI were identified using univariable and multivariable analyses. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to analyze diagnostic performance. RESULTS: Optic nerve enhancement and low ADC of the optic nerve were significant indicators of PLONI. ROC curve analysis showed that the AUC of the combination of these two features for detecting PLONI was 0.87 (95% confidence interval [CI]: 0.78-0.93). The diagnostic performance of this model was significantly superior to that of optic nerve enhancement alone (0.76, 95% CI: 0.65-0.85) and marginally superior to that of the ADC of the affected optic nerve (0.78, 95% CI: 0.68-0.87, P = 0.051). DATA CONCLUSION: Conventional MRI combined with DWI can improve the detection of PLONI in RB patients over conventional MRI alone. EVIDENCE LEVEL: 3 Technical Efficacy: Stage 2.

DIAGNOSTIC YIELD OF IN VITRO VITREOUS BIOPSY FOR INTRAOCULAR LYMPHOMA AT VARIABLE VITREOUS CUTTER SPEEDS USING 25-GAUGE VITRECTOMY.

PURPOSE: Primary vitreoretinal lymphoma is the most common intraocular lymphoproliferative disorder. We evaluated the diagnostic yield of pars plana vitrectomy, specifically using modern high cut rate dual-cycle cutters, on in vitro cell viability and diagnostic yield. METHODS: Human Burkitt lymphoma cell line Namalwa at 2 x 10^5 cells/mL was aspirated by 25-gauge dual-blade guillotine-type vitrectomy at five speeds (500, 1,000, 4,000, 7,500, or 15,000 cuts per minute). Cell viability and diagnostic yield in each subtype group were determined using hemocytometry, viable cell count using Cell Counting Kit-8, and pathologist-guided manual count. RESULTS: No significant deviation in cell count was identified in any cut rate by ANOVA ( P = 0.61), and no trends in the number of viable cells were identified across cut rates (R 2 = 0.188, P = 0.47). Among histologic cell counts per cut-rate, neither linear regression (R = 0.531, P = 0.16) nor ANOVA ( P = 0.096) were statistically significant. CONCLUSION: There was no significant degradation in the number of viable cells with increasing cut speed. These results suggest that in contrast to previous findings using 20g or 23g vitrectomy for diagnostic vitrectomy, modern vitrectomy systems may be used at up to 15,000 cpm without compromising the viability of lymphoma cells.

Polyester 5-0 suture for porous implant placement after retinoblastoma enucleation: analysis of 120 sockets.

BACKGROUND: Techniques used to suture the rectus muscle to the implant can influence the implant-related complications which is still a major problem following retinoblastoma enucleation. The goals of this work were to report the efficacy among patients with retinoblastoma who underwent enucleation followed by porous implant placement with the rectus muscles sutured with 5-0 polyester suture. METHODS: This was a retrospective study of consecutive patients with retinoblastoma who underwent primary enucleation and porous implant placement with the rectus muscles tagged and sutured to the implant with polyester 5-0 suture. All the patients were followed up for a minimum of 2 years. The main outcome measure was implant exposure. The secondary efficacy measures were other implant-related complications. RESULTS: Between May 2016 and December 2018, a total of 120 patients (120 eyes) underwent primary enucleation and porous implant placement were included. Postoperatively, 10/120 (8.3%) eyes developed exposure or conjunctival granuloma. Exposure was the most common postoperative complication (7/10, 70.0%). There were no cases of implant extrusion, migration, or infection. CONCLUSIONS: Polyester 5-0 sutures are successful in patients with retinoblastoma who underwent enucleation followed by porous implant placement. Complications are minimal. Polyester 5-0 sutures were not associated with unacceptable complications in this pediatric population.

Improved Reverse Postauricular Island Flap for Repair of Lower Conjunctival Fornix Retraction.

ABSTRACT: Repair of lower conjunctival fornix retraction is a great challenge for plastic surgeons in the aspects of orbital prosthesis retaining and cosmetic appearance. Hereby, a 25-year-old woman, suffering from lower conjunctival fornix retraction after the removal of retinoblastoma and radiotherapy, was undertaking the treatment with an improved reverse postauricular island flap for expansion of the lower conjunctival fornix, and volume augmentation of the anophthalmic socket in one stage. The flap was based on the parietal branch of the superficial temporal artery and its vascular architecture to the postauricular vascular system, and successfully transferred by passing through a subcutaneous tunnel. The satisfactory result indicated that the mentioned technique may be a good option in surgical rehabilitation of the stable depth of the lower conjunctival fornix, not only from the reliable blood supply and the suitable thickness of the flap but also from the less donor morbidity without an exposed unsightly scar. LEVEL OF EVIDENCE: Level V.

Retinoblastoma associated with orbital pseudocellulitis and high-risk retinoblastoma: a study of 32 eyes.

PURPOSE: To study the correlation between retinoblastoma (RB) associated with orbital pseudocellulitis and high-risk histopathology features. METHODS: Retrospective study of 32 patients who underwent primary enucleation for RB presenting with orbital pseudocellulitis. RESULTS: All RB patients presented with orbital pseudocellulitis. The mean age at presentation of RB was 30 months (median, 24 months; range, 3-70 months). There were 14 (44%) males and 18 (56%) females. All patients were referred with a diagnosis of RB with orbital pseudocellulitis. Tumor was bilateral in 12 (38%) patients but orbital pseudocellulitis was unilateral in all cases. The pseudocellulitis features included proptosis (n = 9; 28%), eyelid edema (n = 22; 69%), conjunctival congestion (n = 23; 72%), and conjunctival chemosis (n = 15; 47%). Based on clinical features and orbital imaging, all patients were diagnosed to have group E intraocular RB. All patients received intravenous steroids prior to enucleation. On histopathology, tumor necrosis was present in all cases with a mean % necrosis of 60% (median, 60%; range, 10% to 90%). Most tumors (72%) were poorly differentiated. High-risk histopathology features were noted in 23 (72%) cases and adjuvant chemotherapy was advised for all these patients. The most common high-risk histopathology features included post-laminar optic nerve infiltration (34%) and scleral infiltration (22%). Over a mean follow-up period of 34 months (median, 9 months; range, < 1-188 months), there was no event of metastasis or death in any patient. CONCLUSION: RB presenting with orbital pseudocellulitis is associated with high incidence of high-risk histopathology features.

Clinical characteristics, treatment and prognosis of children with unilateral retinoblastoma and intracranial segment of Retrobulbar optic nerve invasion.

BACKGROUND: To analyze the clinical characteristics, treatment and prognosis of children with unilateral retinoblastoma (RB) and intracranial segment of retrobulbar optic nerve invasion. METHODS: A total of 14 children with unilateral RB and intracranial segment of retrobulbar optic nerve invasion were enrolled in this retrospective study from January 2009 to December 2018. Clinical characteristics, treatment and prognosis were collected and analyzed. Survival curves were calculated by Kaplan-Meier method. RESULTS: Of 14 cases, there were 7 male and 7 female, ranging in age from 22.85 to 121.97 months (median, 41.03 months). Seventy-one percent of patients came from first-tier cities in China and effected in the left eye. Magnetic resonance imaging (MRI) results indicated that all patients presented with thickened and enhanced optic nerve and intracranial segment of optic nerve invasion. Nine patients received comprehensive therapeutic regimen (chemotherapy, eye enucleation, radiotherapy and intrathecal therapy). The patients were followed up to December 2019, with a median follow-up of 20.6 months. The median disease specific survival was 48.99 ± 8.62 months, and the overall survival (OS) rate was 64.3%. Radiotherapy and comprehensive therapeutic regimen had significant impact on survival time (all p < 0.05). CONCLUSIONS: The overall prognosis of unilateral RB patients with intracranial segment of retrobulbar optic nerve invasion was poor. Chemotherapy and surgical treatment were necessary, but more attention should be paid to radiotherapy and intrathecal therapy for improving prognosis.

Primary orbital polymethylmethacrylate implant following primary enucleation for retinoblastoma: a study of 321 cases.

Purpose: To evaluate the outcome of primary orbital polymethylmethacrylate (PMMA) implant following the primary enucleation for retinoblastoma. Methods: Retrospective study of 321 retinoblastoma patients who underwent unilateral enucleation and PMMA implant for retinoblastoma by myoconjunctival technique. Outcome measures included implant centration and extrusion. Results: The mean age at the time of enucleation of patients with retinoblastoma was 35 months (median, 30 months; range, <1 to 449 months). After primary enucleation, primary orbital PMMA implant was used in all cases. The mean diameter of implant was 18 mm (median, 18 mm; range, 12-20 mm) and the mean horizontal diameter of the socket conformer was 24 mm (median, 24 mm; range, 18 mm-26 mm). Post-enucleation and implant, seven (2%) patients underwent orbital external beam radiotherapy owing to microscopic extrascleral tumor extension or tumor infiltration of optic nerve transection. Over a mean follow-up period of 40 months (median, 34 months; range, 4-129 months), implant migration was noted in 28 (9%) patients, implant extrusion in 9 (3%), and implant exposure in 5 (2%), and contracted socket in 5 (2%) patients including grade 1 contraction in 3 (1%), grade 2 in 1 (<1%), and grade 4 in 1 (<1%) patient. Implant exchange for an improved prosthesis fit was performed in 4 (1%) cases. Stable customized ocular prosthesis was achieved in all but one patient. Conclusion: Primary orbital PMMA implant following primary enucleation for retinoblastoma is associated with minimal complications and provides acceptable cosmetic outcomes.

Next-Generation Sequencing of Retinoblastoma Identifies Pathogenic Alterations beyond RB1 Inactivation That Correlate with Aggressive Histopathologic Features.

PURPOSE: To determine the usefulness of a comprehensive, targeted-capture next-generation sequencing (NGS) assay for the clinical management of children undergoing enucleation for retinoblastoma. DESIGN: Cohort study. PARTICIPANTS: Thirty-two children with retinoblastoma. METHODS: We performed targeted NGS using the UCSF500 Cancer Panel (University of California, San Francisco, San Francisco, CA) on formalin-fixed, paraffin-embedded tumor tissue along with constitutional DNA isolated from peripheral blood, buccal swab, or uninvolved optic nerve. Peripheral blood samples were also sent to a commercial laboratory for germline RB1 mutation testing. MAIN OUTCOME MEASURES: Presence or absence of germline RB1 mutation or deletion, tumor genetic profile, and association of genetic alterations with clinicopathologic features. RESULTS: Germline mutation or deletion of the RB1 gene was identified in all children with bilateral retinoblastoma (n = 12), and these NGS results were 100% concordant with commercial germline RB1 mutation analysis. In tumor tissue tested with NGS, biallelic inactivation of RB1 was identified in 28 tumors and focal MYCN amplification was identified in 4 tumors (2 with wild-type RB1 and 2 with biallelic RB1 inactivation). Additional likely pathogenic alterations beyond RB1 were identified in 13 tumors (41%), several of which have not been reported previously in retinoblastoma. These included focal amplifications of MDM4 and RAF1, as well as damaging mutations involving BCOR, ARID1A, MGA, FAT1, and ATRX. The presence of additional likely pathogenetic mutations beyond RB1 inactivation was associated with aggressive histopathologic features, including higher histologic grade and anaplasia, and also with both unilateral and sporadic disease. CONCLUSIONS: Comprehensive NGS analysis reliably detects relevant mutations, amplifications, and chromosomal copy number changes in retinoblastoma. The presence of genetic alterations beyond RB1 inactivation correlates with aggressive histopathologic features.

Secondary Prevention of Retinoblastoma Revisited: Laser Photocoagulation of Invisible New Retinoblastoma.

PURPOSE: Invisible retinoblastoma tumors are now detected with screening for retinal tumors in at-risk neonates (those inheriting RB1 pathogenic alleles from affected parents) using handheld OCT. Laser photocoagulation is challenging, requiring exact localization of a tumor invisible to indirect ophthalmoscopy and standard imaging. We describe OCT-guided localization and photocoagulation of these invisible tumors with 1-year follow-up. DESIGN: Retrospective, noncomparative, single-institutional, observational case series. PARTICIPANTS: Children with any clinically invisible retinoblastoma tumor that was detected on OCT posterior pole screening. METHODS: OCT revealed round homogeneous invisible tumors within the inner nuclear layer. Software calipers placed beside anatomic retinal landmarks (branched/curved vessels, fovea, or optic disc) mapped the tumor location and extent. A single laser (532 nm) burn flagged the location, and OCT evaluated the tumor-laser burn relationship; laser treatment was then continued in the correct location. Post-laser OCT ensured complete treatment. MAIN OUTCOME MEASURES: Accuracy (frequency of geographic miss and skip areas), effectiveness (recurrence rate), and burden (scar size and characteristics at final follow-up) of laser treatment. RESULTS: Eleven new invisible posterior pole tumors in 7 eyes of 5 children were treated by this technique. Localization and tumor-laser burn relationships were accurate in 11 of 11 tumors (100%, 95% confidence interval [CI], 49.9-100), and all showed swelling and hyper-reflectiveness of the tumor in post-laser OCT. Two photocoagulation sessions (2 weeks apart) were sufficient to successfully manage 9 of 11 tumors (82%, 95% CI, 37.4-100) with resulting permanent flat scars. One tumor (9%, 95% CI, 0.2-50.6) developed OCT-detected subclinical recurrences within 3 months, treated by 1 laser session. No treatment scar showed gliosis, foveal involvement, or retinal traction at 1-year follow-up. Scar expansion occurred in 1 tumor (9%, 95% CI, 0.2-50.6), and all scars (100%, 95% CI, 49.9-100) showed pigmentary changes. CONCLUSIONS: The OCT-guided localization and photocoagulation technique is valuable in achieving precision results in managing invisible new retinoblastoma tumors. This technique shows a potential to improve outcomes of secondary prevention screening for retinoblastoma.

A Multicenter, International Collaborative Study for American Joint Committee on Cancer Staging of Retinoblastoma: Part II: Treatment Success and Globe Salvage.

PURPOSE: To evaluate the ability of the American Joint Committee on Cancer (AJCC) 8th edition to predict local tumor control and globe salvage for children with retinoblastoma (RB). DESIGN: International, multicenter, registry-based retrospective case series. PARTICIPANTS: A total of 2854 eyes of 2097 patients from 18 ophthalmic oncology centers from 13 countries over 6 continents. METHODS: International, multicenter, registry-based data were pooled from patients enrolled between January 2001 and December 2013. All RB eyes with adequate records to allow tumor staging by the AJCC 8th edition criteria and follow-up to ascertain treatment outcomes were included. MAIN OUTCOME MEASURES: Globe-salvage rates were estimated by AJCC clinical (cTNMH) categories and tumor laterality. Local treatment failure was defined as use of enucleation or external beam radiation therapy (EBRT), with or without plaque brachytherapy or intra-arterial chemotherapy (IAC). RESULTS: Unilateral RB occurred in 1340 eyes (47%). Among the 2854 eyes, tumor categories were cT1 to cT4 in 696 eyes (24%), 1334 eyes (47%), 802 eyes (28%), and 22 eyes (1%), respectively. Of these, 1275 eyes (45%) were salvaged, and 1179 eyes (41%) and 400 eyes (14%) underwent primary and secondary enucleation, respectively. The 2- and 5-year Kaplan-Meier cumulative globe-salvage rates without the use of EBRT by cTNMH categories were 97% and 96% for category cT1a tumors, 94% and 88% for cT1b tumors, 68% and 60% for cT2a tumors, 66% and 57% for cT2b tumors, and 32% and 25% for cT3 tumors, respectively. Risk of local treatment failure increased with increasing cT category (P < 0.001). Cox proportional hazards regression analysis confirmed a higher risk of local treatment failure in categories cT1b (hazard ratio [HR], 3.5; P = 0.004), cT2a (HR, 15.1; P < 0.001), cT2b (HR, 16.4; P < 0.001), and cT3 (HR, 45.0; P < 0.001) compared with category cT1a. Use of plaque brachytherapy and IAC improved local tumor control in categories cT1a (P = 0.031) and cT1b (P < 0.001). CONCLUSIONS: Multicenter, international, internet-based data sharing validated the 8th edition AJCC RB staging to predict globe-salvage in a large, heterogeneous, real-world patient population with RB.

HISTOLOGIC FINDINGS IN VITREORETINAL LYMPHOMA: Learning From Enucleation Specimens.

PURPOSE: We aimed to describe the clinical and histologic findings in a few enucleation cases with intraocular lymphoma. METHODS: Retrospective review of pathology files from a 22-year period identified cases with intraocular lymphoma among all enucleation specimens. Patient demographics, clinical findings, laboratory results, radiographic studies, and indication for enucleation were abstracted from electronic health records; slides were reviewed. RESULTS: Four patients (three women and one man; age range, sixth through eighth decades of life) underwent enucleation with a final diagnosis of intraocular lymphoma. Two patients with primary vitreoretinal large B-cell lymphomas had been treated for refractory uveitis. Specimens showed retinal and subretinal infiltrates by atypical large B-lymphocytes and rare neoplastic cells in the vitreous. The remaining two patients had systemic lymphoproliferative disorders. One patient had chronic lymphocytic leukemia and floaters in his eye; vitreoretinal lymphoma developed, consistent with intraocular Richter transformation. The other had diffuse large B-cell lymphoma in remission; however, blurred vision developed, she was treated for panuveitis without improvement, and was later found to have ocular involvement by diffuse large B-cell lymphoma. CONCLUSION: Our series details the unusual circumstances when an eye is removed for intraocular lymphoma. Different patterns of ocular tissue involvement were observed when we compared primary and secondary lymphomas.

VASOPROLIFERATIVE TUMORS IN INTERMEDIATE UVEITIS.

PURPOSE: To describe patients with intermediate uveitis complicated by vasoproliferative tumors (VPTs). METHODS: Data were collected at seven Uveitis/Ocular Oncology centers on demographic, ophthalmic findings at baseline and at follow-up, and on imaging. The therapeutic intervention, final visual acuity, and duration of follow-up were recorded. RESULTS: A total of 36 eyes from 34 patients (12 men, 22 women; mean age 35.3 ± 14.2 years) were included in this study. Visual acuity at presentation ranged from 20/40 to counting fingers. At the time of VPT diagnosis, intermediate uveitis was active in all eyes. The mean VPT thickness was 3.06 ± 0.86 mm. Local treatment to the VPT was provide in 22 eyes (61.1%) and no local treatment to the VPT in 14 eyes (38.9%). After the VPT was detected, systemic or local treatment for the inflammation was initiated and on follow-up FAs 94.4% of the eyes showed resolution of the vascular leakage. During follow-up of 35.8 months, the 22 VPTs treated locally had a reduction in the tumor thickness to 1.25 mm, whereas the 14 VPTs untreated remained stable (final mean tumor thickness 2.65 mm). CONCLUSION: The presence of active intermediate uveitis accompanied by VPTs suggests the need for an aggressive uveitis treatment.

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

BACKGROUND: Optic nerve (ON) invasion is an important high-risk feature, and an indicator for neoadjuvant chemotherapy and prognosis. We aim through this study to correlate the detected-ON invasion by Magnetic resonance imaging (MRI) with the corresponding confirmed histopathological level of invasion. METHODS: A retrospective study of enucleated globes with the diagnosis of retinoblastoma received in the histopathology department(s) from January 2015 to December 2016 (2 years). Slides were reviewed for ON invasion assessment, charts were reviewed for basic demographic data. All patients underwent MRI under sedation upon diagnosis and MRI findings were collected for the above correlation. RESULTS: A total of 38 patients were included: 21 males and 17 females. 29 (77.3%) had unilateral involvement, 7 (18.4%) had bilateral involvement and 2 cases had trilateral disease. The overall mean age at diagnosis was 22.63 ± 15.15 months. Histopathological examination revealed ON invasion in 28 cases (74%) distributed as follows: prelaminar (31.6%), laminar (18.4%), and post-laminar (23.7%). MRI confirmed post-laminar ON invasion in 8 cases (true positive) but failed to detect this in 1 case. Additionally, MRI detected another 8 cases of ON invasion that were false positive on histopathology (accuracy: 63.3%; sensitivity: 88.9%; specificity: 72.4%; Positive predictive value (PPV): 50%; Negative predictive value (NPV): 95.5%). CONCLUSIONS: MRI is found to be less sensitive in evaluating prelaminar and laminar ON invasion (0.0 and 42.9%) compared to post-laminar invasion (88.9%). MRI has generally better specificity in detecting ON invasion irrespective of the invasion level. In our study, obtaining deeper and/or additional histologic sections from the other surface of the tissue block in cases where a post-laminar ON invasion by MRI is found but not confirmed histopathologically in routine sections is essential to avoid missing such an important high-risk feature.

Childhood eye cancer from a parental perspective: The lived experience of parents with children who have had retinoblastoma.

OBJECTIVES: This study aimed to explore the lived experience of parents with children who have had retinoblastoma. METHODS: The study adopted a qualitative approach using the data collection method of written accounts. Eleven parents were recruited via snowball sampling from across the UK. Parents were asked to retrospectively produce a written account of their experiences. These narrative autobiographical accounts were analysed using thematic analysis. RESULTS: Data analysis elicited three themes: waiting and misdiagnosis; emotional rollercoaster; and support needs. Parents described experiencing prolonged periods of waiting from referral to clinical investigations and the implementation of a treatment plan. Difficulties in obtaining an accurate diagnosis for their child elicited anxiety for parents. Emotions were described in terms of a rollercoaster with highs and lows and times of despair, anger, relief, and hope. Experiences of personal support varied and had lasting impacts on relationships. However, the support from other parents with a child with retinoblastoma was perceived to be instrumental in facilitating coping. CONCLUSIONS: The findings show parental experiences were characterised by numerous difficulties and suggest a need for greater awareness of childhood eye cancer. This research highlights the importance of psychological and social support for parents of a child with retinoblastoma.