Surgical management of orbital implant exposures after evisceration or enucleation: Retrospective study - Limoges University Hospital.

INTRODUCTION: Implant exposure is the most frequent complication after evisceration or enucleation, and multiple surgical techniques for the management of orbital implant exposure. The goal of our study is to investigate the success rate and risk factors for failure of various surgical procedures. METHODS: This was a retrospective study performed at the University Hospital of Limoges. We collected data from the files of every patient operated on for implant exposure between January 2005 and December 2020. The main criterion was the percentage of success for each procedure. Secondary objectives were to identify risk factors for failure of Müller's muscle flaps and to determine the incidence of post-enucleation socket syndrome depending on whether the orbital implant was maintained. RESULTS: Fifty-one patients were included: 26 patients who underwent Müller's muscle flap, 16 dermis-fat graft, 3 conjunctival flap, 2 amniotic membrane graft, 1 temporalis fascia graft, 1 buccal mucosa graft, 1 implant rotation, and 1 implant exchange. The dermis-fat grafts were more successful (87.5%) than the Müller's muscle flaps (52.2%) (P=0.0213). The study highlighted the importance of good vascularization of the implant (OR=32.00, P-value=0.0245) for the success of Müller's muscle flaps, and we found no statistically significant difference between the patients who maintained their implants and those who did not (P=0.3865) with regard to the incidence of post-enucleation socket syndrome. CONCLUSION: Müller's muscle flap may remain a reasonable option in the management of medium-sized implant exposures of well-vascularized implants confirmed on MRI in patients with no systemic healing disorders. Dermis-fat graft remains the option of choice in other cases, especially in large exposures or complicated orbits.

Postoperative Pain Following Eye Enucleation: A Prospective Observational Study.

Background and Objectives: Enucleation of an eye is the most invasive procedure in ophthalmologic surgery. It can be the result of various diseases (malignant/chronic/trauma/infection) and is nevertheless relatively rare, but leads to the loss of a strongly innervated neuronal organ. This study systematically evaluates postoperative pain levels following enucleation of the eye globe. Materials and Methods: This prospective single-center study enrolled twenty-four patients undergoing enucleation of the eye globe. Perioperatively all patients completed (preoperative day, day of surgery, 1st, 2nd, and 3rd day following surgery) standardized questionnaires concerning their pain experience and treatment-related side-effects (internal protocol, QUIPS, painDETECT®). Patients received usual pain therapy in an unstandardized individual manner. Results: Preoperatively, mean average pain intensity of all included patients was 3.29 ± 2.46 (range, 0-8), 3.29 ± 3.24 (range, 0-8) on the day of surgery, 4.67 ± 1.90 (range, 2-10) on day 1, 3.25 ± 1.39 (range, 1-6) on day 2, and 2.71 ± 1.30 (range, 1-6) on day 3 after surgery. Mean maximum pain intensity was 4.71 ± 3.28 (range, 0-10) preoperatively, 4.04 ± 3.78 (range, 0-10) on the day of surgery, 5.75 ± 2.01 (range, 2-10) on day 1, 4.25 ± 1.89 (range, 2-10) on day 2, and 3.88 ± 1.54 (range, 2-8) on day 3 after surgery. Nineteen patients (79.2%) stated that they would have preferred more pain therapy. Conclusions: Patients undergoing eye enucleation report pain sensations in need of intervention in this university hospital. Thus, effective standardized pain treatment concepts are now a high priority to be established in an interdisciplinary manner containing standardized regimens and continuous regional procedures. Awareness of this problem in the medical team should be sharpened through targeted training and information.

Does vitreous haemorrhage and calcification lead to increased risk of enucleation in advanced retinoblastoma?

PURPOSE: To explore whether varying degrees of vitreous haemorrhage (VH) and calcification act as risk factors for enucleation in patients with advanced retinoblastoma (RB). METHODS: Advanced RB was defined by the international classification of RB (Philadelphia version). Basic information for retinoblastoma patients diagnosed as groups D and E in our hospital between January 2017 and June 2022 was reviewed by logistics regression models. Additionally, a correlation analysis was performed, excluding variables with a VIF (variance inflation factor) >10 from the multivariate analysis. RESULTS: A total of 223 eyes diagnosed with RB were included in assessing VH and calcification; of these, 101 (45.3%) eyes experienced VH, and 182 (76.2%) eyes were found to have calcification within the tumour through computed tomography (CT) or B-scan ultrasonography. Ninety-two eyes (41.3%) were enucleated, of which 67 (72.8%) had VH and 68 (73.9%) calcification, both of which were significantly relevant to enucleation (p < 0.001*). Other clinical risk factors, such as corneal edema, anterior chamber haemorrhage, high intraocular pressure during treatment and iris neovascularization, correlated significantly with enucleation (p < 0.001*). Multivariate analysis included IIRC (intraocular international retinoblastoma classification), VH, calcification and high intraocular pressure during treatment as independent risk factors for enucleation. CONCLUSIONS: Despite identifying different potential risk factors for RB, there remains significant controversy concerning which patients require enucleation, and the degree of VH varies. Such eyes need to be evaluated carefully, and management with appropriate adjuvant therapy may improve the outcome of these patients.

Surgical outcomes of unwrapped acrylic orbital implants: A review of 192 patients.

PURPOSE: The purpose of this study is to report the results in a series of acrylic orbital implant placements without the use of wrapping material. METHODS: We retrospectively reviewed the records of the patients who underwent enucleation with acrylic orbital implant insertion without scleral wrapping at the Department of Ophthalmology, Poznan University of Medical Sciences, Poland, between 2013 and 2020. RESULTS: There were 192 patients: 102 women and 90 men, mean age: 60 years (range: 13-90 years). In the majority of cases, the reason for enucleation was uveal melanoma (148 patients-77.1%), followed by secondary glaucoma in 22 patients (11.5%) and painful, phthisical eye in 16 (8.3%). The median follow-up was 23 months (range: 1-96 months). The stability of the implants was satisfactory in the majority of cases, and there were no cases of implant migration identified during the study period. We noted a total of 4 (2%) implant exposures. Other postoperative complaints included eyelid malposition-21 patients (11%), Tenon's capsule thinning (15 patients-7.8%) and post-enucleation eye socket syndrome (PEES)-7 patients (3.6%). The rate of postoperative complications was associated only with a history of previous ocular surgery (P=0.006). CONCLUSIONS: The stability and functional outcomes of unwrapped acrylic orbital implants in this group of patients were satisfactory during the follow-up period.

[Epidemiological impact of the COVID-19 pandemic on enucleation cases in Germany]. / Epidemiologische Auswirkungen der COVID-19-Pandemie auf Enukleationsfälle in Deutschland.

PURPOSE: To determine the rate of enucleation in Germany and the impact that the COVID-19 pandemic may have had on its characteristics. METHODS: The rates of enucleation in Germany during 2019 and 2020 were extracted from the diagnosis-related groups (DRG) registry using the operation and procedure classification system codes 5­163.0 through 5­163.23 and 5­163.x. The data were statistically analyzed. RESULTS: The number of enucleations showed a 16.6% reduction from 1295 cases in 2019 compared to 1080 cases in 2020 (p = 0.17). In both years men averaged 54.1% of cases. Patients older than 65 years represented 53% and 56% of cases in 2019 and 2020, respectively. The most common indication for enucleation in both years was phthisis bulbi (n = 373 and n = 307, respectively), accounting for 29.7% of the cases, followed by choroidal malignancies (24%). Enucleation with the simultaneous introduction of an alloplastic orbital implant into Tenon's capsule represented the most common procedure (38.7% combined 2­year average), followed by a sheathed variant (26.6%) and a bulbar implant made of nonabsorbable microporous material (16.8%), without a significant change between years. Enucleations without the introduction of an implant increased from 7.8% in 2019 to 11.1% in 2020 (p = 0.006). The proportion of patients undergoing a reoperation slightly increased from 5.6% to 8% (p = 0.018). Most procedures (65.6%) were performed in large (> 1000 beds) public hospitals. CONCLUSION: Despite the decrease in the total number of procedures performed, the rate of enucleation in Germany was not significantly altered by the COVID-19 pandemic. The rate of enucleation without implants and reoperations significantly increased.

A comparison of high risk pathological features between primary and secondary enucleation for retinoblastoma.

AIM: To compare the risk and pattern of High-Risk Pathologic Features (HRPF) in retinoblastoma between primary and secondary enucleation. METHODS: A retrospective analysis of 121 eyes from 118 patients who underwent enucleation at the King Hussein Cancer Center (KHCC) Amman, Jordan, between November 2009 and January 2020. Demographic information, tumor stage, time from diagnosis-to-enucleation, results of pathology, metastasis, and mortality were retrieved. RESULTS: Patients in the secondary group (49/121 eyes, 40%) were considerably younger at diagnosis (p = 0.0014), had bilateral disease (p = 0.0001), and had less-progressed disease at presentation (p = 0.016) compared to the primary enucleation. Primarily enucleated eyes were more-likely to have massive choroidal invasion (p = 0.0315) and post-laminar optic nerve invasion (p = 0.027), in spite of the finding that the overall prevalence of HRPF was similar between the two groups (35.5 percent vs. 37.5 percent; p = 0.585). The likelihood of anterior chamber invasion, was considerably higher in secondary enucleated eyes (p = 0.013). We evaluated primary and secondary enucleation for each subgroup (D and E) of the International Intraocular Retinoblastoma Classification (IIRC) and found the prevalence of HRPF was comparable (p = 0.58, 1.0, respectively). The difference in time between diagnosis-to-enucleation in secondary enucleation did not predict HRPF (p = 0.50). There was no discernible difference between primary and secondary enucleated eyes in terms of metastasis or survival (p = 0.156 and 0.44, respectively). CONCLUSION: Systemic chemotherapy has the ability to reduce the extent of tumor expansion that has been pathologically identified. Primary and secondary enucleated eyes are comparable in low metastatic risk only when strict examination and management guidelines are followed.

Outcome of eviscerations and enucleations at a Swedish tertiary referral centre between 2008 and 2019: improved surgical management leading to reduced complication rate.

PURPOSE: The aim of this study was to investigate the results of all eviscerations and enucleations performed at the Department of Ophthalmology, Sahlgrenska University Hospital, during 2008-2019 and to compare them with previously collected data from 1999 to 2007. METHODS: This was a retrospective investigation using the medical records for all patients having had an evisceration or an enucleation at the Department of Ophthalmology, Sahlgrenska University Hospital, during the two defined periods of time. Main outcome measure was postoperative complications. RESULTS: During 1999-2007, 181 surgeries were performed, 100 with implants, and 28/100 exposed implants and 9/100 removed implants were recorded during follow-up. During 2008-2019, 250 operations were performed with 158 implants, and there were 3/158 exposed implants and 2/158 extruded implants. Two ruptures of the surgical wound without implant exposure were noted, and one implant was exchanged. The reduction of exposed implants between the two periods was statistically significant (p < .001, Chi-square test). In enucleations, the use of one kind of porous polyethylene implant in the recent study period replaced a multitude of implants in the earlier study period. In eviscerations, the major change between the two study periods was the introduction of the split sclera technique and smaller implant size. CONCLUSION: The change in surgical technique between the two periods led to a significant reduction in implant-related complications.

A Narrative Review - Therapy Options and Therapy Failure in Retinoblastoma.

Retinoblastoma (RB) management has evolved over the last three decades. Goals of modern RB treatment are first to protect life and prevent metastatic disease, then preservation of the globe and useful vision. With modern treatment protocols and early disease detection success rates can reach up to 100% of disease-free-globe and eye preservation. Treatment of advanced cases remains complex, requiring aggressive chemotherapy or/and external beam radiation. Treatment protocols are extremely diverse and dependent on local resources thus success rates are variable. Here we review narratively current treatment protocols and failure rates based on a PubMed search using keywords of retinoblastoma, retinoblastoma seed, retinoblastoma treatment, enucleation.

The anatomic classification of the anophthalmic eye socket (Types 0-V): A high-level taxonomy classification system.

Eyelid and orbital deformities caused by various defects, such as tumor resection and trauma, whether congenital or acquired, are extremely complex and atypical. Several classifications systems for these anophthalmic conditions have been developed, but none have proven suitable for determining the ideal reconstructive surgical strategy. We therefore designed a novel system known as the Anatomic Classification of the Anophthalmic Eye Socket (Types 0-V) for optimum reconstruction of anophthalmic socket deformities focusing on eyelid and orbital defects. Type 0 is an eyelid defect type, in which only the eyelid is defective; Type I is a phthisis bulbi type, in which the anatomical eyeball is preserved, but the visual function is lost; Type II is a substitution type involving filling with implant packing after evisceration or enucleation; Type III is an enucleation type involving enucleation of the ophthalmus; Type IV is an exenteration (incomplete) type involving exenteration while saving the eyelids; and Type V is an exenteration (complete) type involving exenteration including eyelid defects. Using this classification system, it will be possible to standardize reconstructive procedures of the anophthalmic socket.

Cosmetic Outcome Of Autogenous Dermis Fat Graft As An Orbital Implant After Enucleation.

BACKGROUND: The surgical method of removing the complete intact globe while leaving the extraocular muscles and orbital fat behind is called as enucleation. The intention behind this study is to share the experience of autogenous dermis fat graft as an orbital implant following enucleation and its cosmetic outcome. It was a prospective study conducted at the Orbit and Oculoplastic department of LRBT Tertiary Teaching Eye hospital from July 2018 to June 2019. Methods: Eighty-five patients were recruited for this study belonging to either gender with ages ranging from 20 to 50 years. None of the recruited patients had undergone prior enucleation or evisceration. All the patients were informed and counseled about the surgical modus operandi and the expected outcomes and verbal consent was taken from each patient along with approval from the hospital's ethical review committee before proceeding with the surgery. Every participant underwent primary enucleation followed by autogenous dermis fat graft orbital implant and followed up for duration of up to 3 months after the surgical procedure. Results: At ninety days after the procedure, 78.2% of patients had a very good cosmetic result. Conclusion: The placement of autogenous dermis fat graft as an orbital implant following primary enucleation has a good accomplishment rate with excellent cosmetic outcome.

Case series of shrinking hydroxyapatite orbital implants.

BACKGROUND: An orbital implant is used after enucleation or evisceration surgery to replace the volume lost and to aid in prosthesis fitting and movement. Different materials have been used through the years. The authors noted that with bone-derived hydroxyapatite orbital implants, some patients lose their orbital volume. METHODS: The operating theatre record was searched to find patients who had their hydroxyapatite orbital implant removed at Dunedin Hospital, New Zealand, between 2011 and 2015. The original implant size and size at removal were noted. Histological results were noted. Medical notes were reviewed. RESULTS: A total of six patients had hydroxyapatite orbital implants removed during this time. Four patients had implants that were smaller than their original sizes. All specimens had fibrovascular infiltration noted, three had chronic inflammatory cells and one had osteoclastic activity. CONCLUSIONS: Bone-derived hydroxyapatite orbital implants can reduce in size, and this may occur due to osteoclastic activity. The surgeon must consider this scenario when choosing the type of implant to be used after enucleation or evisceration.

Globe salvage treatment in group D and group E retinoblastoma.

Importance: Globe salvage marks the treatment success of retinoblastoma. Background: To evaluate four treatment strategies in group D and group E retinoblastoma. Design: Retrospective case series in a tertiary hospital. Participants: 81 patients with Group D and Group E retinoblastoma. Methods: Participants were divided into four sets. In set I, eyes received primary intravenous chemotherapy (IVC), cryotherapy (CT), laser therapy (LT) and Intravitreal Chemotherapy with Melphalan (IViC). In set II, primary IVC was combined with second line IVC, CT, LT and IVT-M. Set III eyes received primary IVC and Intra-arterial chemotherapy (IAC), CT, LT and IViC. Set IV eyes received IAC, CT, LT and IViC. Treatment failure was defined as inadequate response during or after IVC or IAC. Main Outcome Measures: globe salvage and enucleation rates. Results: 52 eyes were included in group D and 29 in group E. In group D, globe salvage was obtained in 8 out of 11 eyes in Set I, 13 out of 19 eyes in set II, 5 out 6 eyes in set III, and 13 out of 16 eyes in set IV. In group E, enucleation was performed in 17 eyes. Global salvage was obtained in 0 out of 2 eyes in set I, 2 out of 3 eyes in set II, 3 out of 5 in set III, and in 1 out of 2 eyes in set IV. Conclusions: IVC with adjuvant IAC, LT, CT and IViC has shown favorable results as a treatment method for group D and group E retinoblastoma.

Streptococcus pneumoniae endophthalmitis: clinical settings, antibiotic susceptibility, and visual outcomes.

Streptococcus pneumoniae endophthalmitis is clinically more severe, more difficult to treat, and carry a higher risk of vision loss, evisceration, or enucleation. This study is to investigate the clinical settings, antibiotic susceptibility, and visual outcomes of S. pneumoniae endophthalmitis at a tertiary referral center in Taiwan. S. pneumoniae endophthalmitis was diagnosed in 38 eyes of 38 patients. The main clinical features were postcataract endophthalmitis (n = 13, 34%) and endophthalmitis associated with corneal ulcer (n = 12, 32%), trauma (n = 6, 16%), endogenous etiology (n = 4, 11%), trabeculectomy (n = 2, 5%), and pterygium excision-related scleral ulcer (n = 1, 3%). Presenting visual acuity ranged from counting fingers to no light perception. Pars plana vitrectomy with intravitreal antibiotics was performed in 17 eyes (39%) in primary or secondary treatments. S. pneumoniae isolates were susceptible to vancomycin (38/38, 100%), penicillin (37/38, 97%), ceftriaxone (37/38, 97%), cefuroxime (12/15, 80%), levofloxacin (13/15 ,87%), and moxifloxacin (15/17, 88%). Final visual acuity was better than 20/400 in 3 of 38 eyes (8%), 5/200 to hand motions in 3 eyes (8%), and light perception to no light perception in 32 eyes (84%). Ten eyes (26%) underwent evisceration or enucleation. Although S. pneumoniae isolates were susceptible to vancomycin, S. pneumoniae endophthalmitis had a very poor visual prognosis.

Aberrant development of excitatory circuits to inhibitory neurons in the primary visual cortex after neonatal binocular enucleation.

The development of GABAergic interneurons is important for the functional maturation of cortical circuits. After migrating into the cortex, GABAergic interneurons start to receive glutamatergic connections from cortical excitatory neurons and thus gradually become integrated into cortical circuits. These glutamatergic connections are mediated by glutamate receptors including AMPA and NMDA receptors and the ratio of AMPA to NMDA receptors decreases during development. Since previous studies have shown that retinal input can regulate the early development of connections along the visual pathway, we investigated if the maturation of glutamatergic inputs to GABAergic interneurons in the visual cortex requires retinal input. We mapped the spatial pattern of glutamatergic connections to layer 4 (L4) GABAergic interneurons in mouse visual cortex at around postnatal day (P) 16 by laser-scanning photostimulation and investigated the effect of binocular enucleations at P1/P2 on these patterns. Gad2-positive interneurons in enucleated animals showed an increased fraction of AMPAR-mediated input from L2/3 and a decreased fraction of input from L5/6. Parvalbumin-expressing (PV) interneurons showed similar changes in relative connectivity. NMDAR-only input was largely unchanged by enucleation. Our results show that retinal input sculpts the integration of interneurons into V1 circuits and suggest that the development of AMPAR- and NMDAR-only connections might be regulated differently.

Open-globe wounds in operation Iraqi Freedom and Operation Enduring Freedom: risk factors for poor visual outcomes and enucleation.

PURPOSE: To determine the rates and types of open-globe wounds in soldiers admitted to Walter Reed Army Medical Center from 2001 to 2011 after sustaining combat injuries. METHODS: Data were collected in the Walter Reed Ocular Trauma Database. Inclusion criteria were patients who suffered open-globe injuries. Open-globe injuries were classified by type of wound: corneal, corneo-scleral or scleral, or type of open-globe injury: perforating, rupture, penetrating or intraocular foreign body. The primary analysis assessed the effect on final visual acuity (VA) and the risk of enucleation. RESULTS: In this study, 285 (32.02%) open-globe injuries were recorded in 890 eyes in the data set. Corneal wounds were noted in 127 (44.56%) eyes, corneo-scleral wounds in 78 (27.37%) and scleral wounds in 129 (45.26%) eyes. The involvement of both the corneal and sclera was associated with poorer visual outcome (BCVA < 20/200) compared to injuries with an injury confined to either the cornea or scleral alone (p = 0.038). At a wound length of greater than approximately 14 mm, patients had 75% chance of having a poor final VA. Enucleation was performed in 64 (22.46%) eyes of patients with wounds. The type of wound was not found to be predictive of enucleation in multivariate analysis, but rather the type of open-globe injury was predictive. Perforating (OR: 1.58, 95% CI: 1.43-1.72) and globe rupture injuries (OR: 1.49, 95% CI: 1.33-1.66) were more likely to undergo enucleation. CONCLUSIONS: Open-globe injuries occur frequently in combat ocular trauma. Poor final VA was noted most with corneo-scleral wounds with approximately 50% of patients having a final VA less than 20/200.

Multidisciplinary Approach for Retinoblastoma Management.

We read with keen interest the article by Shah et al "Pathologic Risk Factor in Retinoblastoma: An Institutional Experience Based on Analysis of Enucleated Eyes"(Shah A et al, 2012). They have highlighted high-risk histopathological features in Retinoblastoma with retrolaminar optic nerve invasion being the most common and also showed statistically significant correlation of high risk histological features with tumor size and AJCC stage of tumor. Their aim to assess the frequency and spectrum of high risk histopathological features in enucleated specimens of retinoblastoma was successful which may guide the clinician in timely planning for subsequent neoadjuvant therapy and prevent further ocular morbidity and mortality in children. We would like to congratulate authors for this article and with invoked interest it led us to go in more depth and we wish to discuss several aspects of the study that can potentially influence the results.

Traumatic avulsion of the globe with optic nerve transection: an unusual presentation.

Complete globe extrusion, whether traumatic or spontaneous, is a rare clinical entity and if associated with optic nerve avulsion, it has a worse visual outcome, though repositioning of the globe may be attempted. We report a case of road traffic accident, wherein the patient presented with an extrusion of the globe, along with a complete transection of the optic nerve, about 4 cm from the optic nerve head, with only a residual attachment to the orbital rim via the unsevered lateral conjunctival flap, where the enucleation was completed and the conjunctiva was sutured.

Adenoma and Adenocarcinoma of the Retinal Pigment Epithelium: A Review of 51 Consecutive Patients.

PURPOSE: To describe the clinical and imaging characteristics, pathologic features, and management options of retinal pigment epithelium (RPE) adenoma/adenocarcinoma. DESIGN: Retrospective case series. PARTICIPANTS: Fifty-one patients with RPE adenoma/adenocarcinoma. METHODS: Treatment options for the patients included observation, partial lamellar sclerouvectomy (PLSU), enucleation, and others. MAIN OUTCOME MEASURES: Factors related to visual acuity (VA) outcomes (>2 Snellen lines loss, poor final VA [≤20/200], good final vision [≥20/40]), tumor growth, and need for enucleation. RESULTS: The mean patient age at diagnosis was 51 years, and the majority of patients were white (40/51, 78%) and female (34/51, 67%). Primary management included observation (29/51, 57%), PLSU (9/51, 18%), enucleation (4/51, 8%), or others (9/51, 18%). Outcomes revealed decreased VA (10/32, 31%), poor final VA (17/32, 53%), good final VA (11/32, 34%), tumor growth (12/25, 48%), and need for enucleation (7/51, 14%). By multivariable analysis, features predictive of decreased VA included increasing baseline tumor thickness (P = 0.01) and presence of vitreous hemorrhage (P = 0.05). Factors predictive of poor final VA included presence of exudative retinal detachment (P = 0.004), baseline VA 20/50 to 20/150 (P = 0.008), and baseline VA ≤20/200 (P = 0.01). Absence of feeding and/or draining vessel was predictive of good VA (P = 0.004). Tumor growth was associated with multiple treatments (P = 0.02). Increased tumor thickness (P = 0.03) and presence of exudative retinal detachment (P = 0.01) were predictive of enucleation. CONCLUSION: RPE adenoma/adenocarcinoma can simulate choroidal melanoma. Greater tumor thickness, vitreous hemorrhage, exudative retinal detachment, and poor baseline VA predict worse visual outcome and greater risk for enucleation.

Molecular profiling of vitreous fluid by massively parallel sequencing: a case series.

INTRODUCTION: In cases of suspected intraocular malignancy, vitreous may be the preferred pathologic sample; however, cellularity may be insufficient for definitive cytopathological diagnosis. Ancillary methodology to study vitreous fluid aspiration for mutational analysis may assist in treatment decisions. MATERIALS AND METHODS: Three individual patient vitreous humor samples were received in the laboratory for mutation testing. The samples were collected during standard of care and analyzed for routine cytopathology. In each case, cytopathology was inconclusive and mutational analyses to support diagnostic suspicions were clinically requested. Based on the clinically and pathologically suspected diagnoses, an appropriate massively parallel sequencing assay previously validated for clinical use was performed using DNA extracted from vitreous samples that had previously undergone various processing. Nucleic acid yield was assessed by fluorometric or spectrophotometric methods, with yield ranging from 2.7 to 86.5 ng. Library preparations were performed using standard laboratory protocols. RESULTS: Two of the cases were suspicious for melanoma and a 50-gene solid tumor panel was performed. The third case was worrisome for vitreoretinal lymphoma and a 49-gene myeloid panel was performed. CONCLUSIONS: In all cases, the molecular profiling assisted with the clinical assessment and/or management of each patient.

Impact of Systemic Chemotherapy and Delayed Enucleation on Survival of Children with Advanced Intraocular Retinoblastoma.

PURPOSE: Primary enucleation is a well-established method to achieve cure for advanced intraocular retinoblastoma. Recent treatment advances have induced a trend toward trial eye salvage using chemotherapy or other modalities. We investigated how pre-enucleation/postenucleation systemic chemotherapy and the resulting delayed enucleation affect patient survival after failed trial eye salvage. DESIGN: Multicenter, retrospective cohort study. PARTICIPANTS: Children with Group D and E retinoblastoma primarily or secondarily enucleated at 29 Chinese treatment centers. METHODS: Data reviewed included clinical staging, time from diagnosis to enucleation, numbers of cycles of carboplatin, etoposide/teniposide and vincristine chemotherapy, disease-specific survival (DSS), histopathology, and follow-up. MAIN OUTCOME MEASURES: Primary outcome was DSS. Secondary outcome was histopathology of enucleated eyes. RESULTS: Primarily enucleated eyes had significantly shorter delay from diagnosis to enucleation than eyes treated with pre-enucleation chemotherapy (P < 0.001). Delay between diagnosis and enucleation >3.5 months (Group D) and >2 months (Group E) decreased survival (Group D: P = 0.018; Group E: P = 0.017). Compared with primarily enucleated children, children with 1 to 3 cycles of pre-enucleation chemotherapy for Group E eyes had no significant difference in survival (P = 0.74), but those who received ≥4 cycles had worse survival (P = 0.025). After pre-enucleation chemotherapy, more children with Group E (but not Group D) eyes had high-risk histopathology (pT3/pT4) (Group D: P = 0.076; Group E: P < 0.001) and worse survival than those primarily enucleated (P < 0.001). Postenucleation chemotherapy improved survival of children with high-risk histopathology (pT3/pT4) (P = 0.001) but did not change survival of children with low-risk histopathology (pT1/pT2) (P = 0.52). CONCLUSIONS: We observed that pre-enucleation chemotherapy offered no survival benefit and timely enucleation minimized risk of metastatic death. Postenucleation chemotherapy improved survival of children with high-risk histopathology but was not useful for those with low-risk histopathology. These findings facilitate informed discussion on the risks and benefits of delayed enucleation, the use of systemic chemotherapy for trial salvage of eyes with advanced intraocular retinoblastoma, and the specific children who benefit from postenucleation chemotherapy.