Differences in Childhood Growth Parameters Between Patients With Somatic and Heritable Retinoblastoma.

Purpose: Little is known regarding differences in childhood growth between somatic and heritable retinoblastoma (Rb) populations. We aimed to compare childhood growth parameters between somatic and heritable Rb cohorts at birth and at time of diagnosis with Rb. Methods: A multinational, longitudinal cohort study was conducted with patients from 11 centers in 10 countries who presented with treatment naïve Rb from January to December 2019. Variables of interest included age, sex, and size characteristics at birth and at time of presentation, as well as germline mutation status. After Bonferroni correction, results were statistically significant if the P value was less than 0.005. Results: We enrolled 696 patients, with 253 analyzed after exclusion criteria applied. Between somatic (n = 39) and heritable (n = 214) Rb cohorts, with males and females analyzed separately, there was no significant difference in birth weight percentile, weight percentile at time of diagnosis, length percentile at time of diagnosis, weight-for-length percentile at time of diagnosis, or change of weight percentile from birth to time of diagnosis. Patients with heritable Rb had a smaller mean weight percentile at birth and smaller mean weight and length percentiles at time of diagnosis with Rb, although this difference was not statistically significant. All cohorts experienced a slight negative change of weight percentile from birth to time of diagnosis. No cohort mean percentiles met criteria for failure to thrive, defined as less than the 5th percentile. Conclusions: Children with Rb seem to have normal birth and childhood growth patterns. There is no definitive evidence that somatic or heritable Rb has a biological or environmental impact on childhood growth parameters.

PATIENT-RELATED FACTORS AND CLINICAL MANAGEMENT OUTCOMES OF RETINOBLASTOMA IN CALABAR, NIGERIA.

Background: Retinoblastoma is curable in industrialized countries. However, it is associated with mortality in resource-poor nations due to disparities and poor access to eye care. Aim was to determine the relationships between patient-related factors and clinical outcomes of Retinoblastoma management in a tertiary hospital in Nigeria. Materials and methods: This was a retrospective study of all children who were diagnosed and treated for Retinoblastoma from January 2017 through December 2022. Information obtained from their records included biosocioeconomic data, symptoms, lag time from initial symptoms, staging, treatment and outcome (dead or alive). Results: Fifty-three patients, aged 6 to 88 months on first hospital presentation were recruited. There were 29(54.7%) females and 20(37.7%) patients died. Parental low socioeconomic class, rural residence and poor nutrition occurred more in those that survived, though not significantly (p>0.05). Median(interquartile) age at diagnosis [24(18-36) months, p=0.005] and lag time [13(6-20) months, p=0.274] were low in the survived group. Bilateral Retinoblastoma (20.8%,p=0.002), brain metastasis (22.6%,p<0.001), IRSS IV (18.9%,p=0.01) and relapse (34%,p<0.001) occurred more among the patients that died. The overall survival (OS) was 22(11.77-32.23) months with 1-year OS of 63%. Treatment with only chemotherapy [HR 4.76(95%CI:1.726-13.128)], incomplete chemotherapy [HR 5.61(95%CI:1.271-24.741)], relapse [HR 5.98(95%CI:1.376-25.983)] and eye surgery after 3 chemotherapy cycles [HR 8.22(95%CI:1.087-62.239)] were predictors of mortality. Conclusion: Early presentation of retinoblastoma especially of advanced and bilateral disease may lead to improved survival if chemotherapy and eye surgery are appropriately performed. Routine screening and immediate referral of retinoblastoma particularly in rural areas are recommended.

Strabismus in retinoblastoma survivors with long-term follow-up.

PURPOSE: To report the long-term strabismus rate in salvaged retinoblastoma (Rb) patients and investigate possible risk factors leading to strabismus. METHODS: The medical records of patients with Rb presenting at a single institution over a 9-year period were reviewed retrospectively with regard to ocular alignment outcomes after long-term follow-up. RESULTS: A total of 64 eyes of 42 patients (22 bilateral cases [52%]) were included, presenting with International Intraocular Retinoblastoma Classification (IIRC) in the worse eye as follows: group A (n = 1), B (n = 16), C (n = 12), D (n = 11), no Rb (n = 2). Fifteen patients (36%) were initially referred because of family history of Rb. Mean age at presentation was 8.2 months (range, 0.3-58.3 months). Overall treatments included intravenous chemotherapy (62 eyes), intraophthalmic artery chemotherapy (10 eyes), brachytherapy (11 eyes), transpupillary thermotherapy (22 eyes), cryotherapy (47 eyes), and external beam radiotherapy (4 eyes). At final follow-up (mean, 93.7 months), 69% of patients had strabismus, with exotropia being the most common type (n = 18), followed by esotropia (n = 8), and alternate exotropia/esotropia (n = 3). On univariate analysis, the worse eye group IIRC and cTNMH, sporadic cases, strabismus, and foveal tumor at presentation were found to be significantly associated with strabismus at final follow-up (P ≤ 0.043). On multivariate analysis, only foveal involvement was found to be significant (P < 0.001). CONCLUSIONS: Strabismus, exotropia in particular, is a common adverse sequela following successful conservative treatment for Rb, with 69% of the present cohort having some type of deviation after long-term follow-up, for which foveal tumor at presentation was found to be a significant risk factor.

The management of retinoblastoma.

Retinoblastoma (Rb) is the most common primary intraocular malignancy of childhood, but an uncommon paediatric cancer, with a constant incidence worldwide of 1:15,000-1:20,000 live births. Despite its rarity, Rb has served as a cornerstone in the field of oncology in many of the aspects that comprise cancer management, including classification schemes, treatment modalities, genetic testing and screening. Until just over half a century ago, the major treatment for Rb was eye removal, and prognosis was poor with outcome fatal for most children. The dramatic evolution, in a short period of time across all fields of Rb management, as well as the development of specialized centres, better infrastructure and introduction of awareness campaigns, has resulted in nearly 100% survival in developed countries and allowed eye salvage in many of the cases. External beam radiotherapy was used as the main treatment choice for four decades, but replaced by chemotherapy at the turn of the century. Initially, and still in many centres, chemotherapy is administered intravenously, but recently is targeted directly into the eye by means of intra-ophthalmic artery and intravitreal chemotherapy. To date, a range of treatments is available to the Rb expert, including enucleation, but there is lack of consensus in a number of scenarios as to what to use and when. In such a rare cancer, treatment outcomes are reported usually via retrospective analyses, with few prospective randomized controlled trials. Classification schemes have also evolved following the introduction of new treatment modalities, but discrepancies exist among centres with respect to the preferred schema and its interpretation. Retinoblastoma management is a remarkable success story, but the future will require a collaborative effort in the form of multicentre randomized controlled trials in order to further improve the quality of care for this subset of young children with ocular cancer.

Primary enucleation for group D retinoblastoma in the era of systemic and targeted chemotherapy: the price of retaining an eye.

BACKGROUND: Chemotherapy is increasingly used as primary treatment for group D retinoblastoma, whereas primary enucleation is considered to have a diminishing role. This study aimed to compare the management course, including number of examinations under anaesthesia (EUAs), of group D patients treated by enucleation versus chemotherapy. METHODS: A retrospective analysis of 92 group D patients, of which 40 (37 unilateral) underwent primary enucleation and 52 (17 unilateral) were treated with intravenous chemotherapy. Number of EUAs was compared between the treatment groups with respect to the whole cohort, using univariate and multivariate analysis, and to unilateral cases only. RESULTS: Patients were followed up for a median of 61 months (mean: 66, range: 14-156), in which time primary enucleated patients had on average seven EUAs and chemotherapy-treated patients 21 EUAs (p<0.001). Chemotherapy, young age, bilateral disease, multifocal tumours, familial and germline retinoblastoma were found on univariate analysis to correlate with increased number of EUAs (p≤0.019). On multivariate analysis, however, only treatment type and presentation age were found significant (p≤0.001). On subanalysis of the unilateral cases, patients undergoing primary enucleation had in average seven EUAs, as compared with 16 in the chemotherapy group (p<0.001). Of the 55 unilateral-presenting patients, a new tumour developed in the fellow eye only in a single familial case. CONCLUSION: Group D patients' families should be counselled regarding the significant difference in number of EUAs following primary enucleation versus chemotherapy when deciding on a treatment strategy. In this regard, primary enucleation would be most beneficial for older patients with unilateral disease.

Focal laser treatment in addition to chemotherapy for retinoblastoma.

BACKGROUND: Retinoblastoma is the most common primary intraocular malignancy of childhood. Systemic chemotherapy is a common treatment for intraocular retinoblastoma, and laser treatment is used as adjuvant therapy during or immediately after chemotherapy courses in selected cases. OBJECTIVES: To compare the effectiveness and safety of adding focal laser therapy to systemically-delivered chemotherapy in treating intraocular retinoblastoma. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 9), MEDLINE Ovid (1946 to 20 October 2016), Embase Ovid (1980 to 20 October 2016), LILACS (Latin American and Caribbean Health Sciences Literature Database) (1982 to 20 October 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch); searched 20 October 2016, ClinicalTrials.gov (www.clinicaltrials.gov); searched 20 October 2016, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 20 October 2016. We did not use any date or language restrictions in the electronic searches for trials. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) of systemic chemotherapy with versus without adjuvant laser therapy for postequatorial retinoblastoma. DATA COLLECTION AND ANALYSIS: We planned to use standard methodological procedures expected by Cochrane. We planned to meta-analyse the primary outcome, that is the proportion of eyes with recurrence of tumours within three years from treatment MAIN RESULTS: No studies met the inclusion criteria for this review. AUTHORS' CONCLUSIONS: No evidence from randomised controlled trials was found to support or refute laser therapy in addition to systemic chemotherapy for postequatorial retinoblastoma.

Long-term Visual Acuity, Strabismus, and Nystagmus Outcomes Following Multimodality Treatment in Group D Retinoblastoma Eyes.

PURPOSE: To analyze the long-term visual acuity, strabismus, and nystagmus outcomes in Group D retinoblastoma following multimodality treatments in a national retinoblastoma referral center. DESIGN: Retrospective interventional case series. METHODS: A 13-year retrospective chart review of Group D eyes treated initially with intravenous chemotherapy (IVC) and followed up for at least 1 year from last treatment. Risk factors for final visual acuity (VA) were analyzed, and rate of strabismus and nystagmus at last follow-up visit were calculated. RESULTS: One hundred and four Group D eyes (92 patients) presented to our center during the study period, of which 32 (27 patients) met the inclusion criteria. Following IVC (vincristine, etoposide, and carboplatin), adjuvant treatments included intraophthalmic artery chemotherapy in 5 (16%) eyes, plaque brachytherapy in 5 (16%), transpupillary thermotherapy (TTT) in 18 (56%), and cryotherapy in 24 (75%) eyes. On last examination, 64.41 ± 6.76 months from presentation, mean final VA was 20/283 (logMAR equivalent of 1.15 ± 0.15). On univariate analysis, presentation age, foveal retinoblastoma (at initial examination), use of TTT, and tumor-foveola distance (at last visit) were found to be significant risk factors for worse VA (P < .026). On multivariate analysis, however, only TTT was found to be significant (P = .010). At last visit, 6 of 27 (22%) patients had nystagmus and 12 of 20 (60%) bilaterally salvaged patients had strabismus (n = 10 exotropia and n = 2 esotropia). CONCLUSIONS: After multimodality treatments initiated with IVC, 50% of salvaged Group D retinoblastoma eyes had <20/200 vision, with TTT being a risk factor for worse vision; 60% had strabismus; and 22% had nystagmus.

High-Risk Histopathology Features in Primary and Secondary Enucleated International Intraocular Retinoblastoma Classification Group D Eyes.

PURPOSE: To evaluate the rate and identify the risk factors for high-risk histopathologic features in group D retinoblastoma eyes enucleated as primary or secondary treatment. DESIGN: Retrospective analysis. PARTICIPANTS: A total of 64 enucleated group D eyes (62 patients), of which 40 (40 patients) were primary and 24 (22 patients) were secondary to other treatments. METHODS: Clinicopathologic correlation of consecutive group D eyes enucleated from 2002 to 2014. High-risk histopathologic features were defined as the presence of anterior chamber seeds, iris infiltration, ciliary body/muscle infiltration, massive (≥3 mm) choroidal invasion, retrolaminar optic nerve invasion, or combined non-massive choroidal and prelaminar/laminar optic nerve invasion. MAIN OUTCOME MEASURES: High-risk histopathologic features, metastasis, and death. RESULTS: Of the 64 group D eyes, 37 (58%) were classified as cT2bN0M0H0, 24 (38%) were classified as cT2bN0M0H1, and 3 (5%) were classified as cT2aN0M0H1, according to the 8th edition cTNMH Retinoblastoma Staging. High-risk histopathologic features were detected in 10 eyes (16%) in the entire cohort, 5 eyes (13%) of the primary enucleated group (pT3aNxM0, n = 2 and pT3bNxM0, n = 3, 8th edition pTNM), and 5 eyes (21%) of the secondary enucleated group (pT2bNxM0, n = 2, pT3aNxM0, n = 2 and pT3cNxM0, n = 1). Absence of vitreous seeds at presentation was the only predictive factor found for high-risk histopathologic features in the primary enucleation group (P = 0.042), whereas none were found in the secondary group (P ≥ 0.179). Invasion of the anterior structures (anterior chamber, iris, ciliary body/muscle) was detected significantly more after secondary enucleation (P = 0.048). All patients with high-risk histopathologic features were treated with adjuvant chemotherapy, and no metastases were recorded in a median follow-up time of 73.2 months (mean, 71.5; range, 13.7-153.0). CONCLUSIONS: The choice of primary treatment for group D retinoblastoma should be carefully weighed, because according to this study, 13% of eyes harbor high-risk histopathologic features at presentation, with the absence of vitreous seeds being a potential risk factor. It is of special importance in group D eyes being considered for nonsystemic treatment, such as primary intraophthalmic artery chemotherapy. Secondary enucleated group D eyes with high-risk histopathologic features more commonly involved anterior structures, warranting meticulous clinical and histologic examinations for this subset of patients.

Ocular oncology: advances in retinoblastoma, uveal melanoma and conjunctival melanoma.

Background: Retinoblastoma, uveal and conjunctival melanomas are important malignancies within the remit of ocular oncology. Outlined are the diagnostic features and management principles, as well as advancements in the field and current challenges. Sources of data: Original papers, reviews and guidelines. Areas of agreement: Most eyes with retinoblastoma (International Intraocular Retinoblastoma Classification (IIRC) Group A-D) are salvaged, whereas advanced cases (Group E) remain a challenge. Despite a high rate of local tumour control in uveal melanoma, metastatic spread commonly occurs. Conjunctival melanoma is treated by complete resection, but high rates of local recurrence occur, with the possibility of systemic relapse and death. Areas of controversy: Use of the IIRC in retinoblastoma, and systemic screening in melanomas. Growing points: Utilization of novel treatment modalities in retinoblastoma and an increasing understanding of the genetic basis of melanomas. Areas timely for developing research: Improvements in chemotherapy delivery in retinoblastoma and prognostic tests in melanomas.

Primary intravenous chemotherapy for group D retinoblastoma: a 13-year retrospective analysis.

BACKGROUND: Eye salvage rate for group D retinoblastoma using intravenous chemotherapy (IVC) as a primary modality is <50%. To report on 13 years' experience with the use of primary IVC for group D retinoblastoma. METHODS: A retrospective analysis of 64 group D eyes (52 patients) treated with primary IVC, from 2002 to 2014. RESULTS: The median age at presentation was 11.0 months (mean: 18.6, range: 0.6-144.0), 35 (67%) patients had bilateral disease, 38 (73%) germline disease and 8 (15%) cases were familial. In addition to IVC, patients received a median number of three treatments (mean: 6, range: 0-24), including thermotherapy/cryotherapy, plaque radiotherapy, intra-ophthalmic artery chemotherapy (IAC) and/or intravitreous chemotherapy. External beam radiotherapy (EBRT) was used in five eyes, all of which were eventually enucleated. In a median follow-up time of 55 months (mean: 64, range: 14-156), 63% of eyes were salvaged. By the Kaplan-Meier survival analysis, globe salvage rate was 83%, 70%, 59% and 45% at 1, 3, 5 and 10 years, respectively. There were no cases of metastatic spread from intraocular retinoblastoma and no deaths. IVC-related adverse events included febrile neutropenia in 21 (40%) patients and anaphylactic reaction to carboplatin in 2 (4%), all conservatively resolved. Of the patients receiving IAC, third and sixth nerve palsies were documented in two (10%) and one (5%) eyes, respectively. CONCLUSIONS: Primary IVC for group D eyes, with adjuvant treatments as required, was found to be a safe and efficient approach, achieving 63% eye salvage rate, no metastatic spread from intraocular retinoblastoma and no deaths. IAC has now replaced EBRT as a successful salvage treatment.

Acute Optic Neuropathy and Development of Posttraumatic Stress Disorder.

This study aimed to determine the prevalence and risk factors of posttraumatic stress disorder (PTSD) in 171 acute optic neuropathy (AON) patients, and to compare the findings to those previously reported on 366 rhegmatogenous retinal detachment (RRD) patients. PTSD positively screened AON patients underwent a structured psychiatric interview and a Visual Function Questionnaire (VFQ). Clinical measures were retrieved from medical records and compared between cohorts. None of the AON patients was diagnosed with PTSD, as opposed to 2.5% of RRD patients (P = 0.063). Of the AON cohort, 34% of patients were administered steroids, compared to none of the RRD patients, whereas all of the RRD patients underwent surgery, compared to none of the AON patients (P < 0.001). Clinical measures and VFQ scores were not found as risk factors for PTSD prediction. Results imply the potential role of surgery and of steroid treatment in developing PTSD in cases of ocular insults.

MALIGNANT TRANSFORMATION OF A CHOROIDAL NEVUS IN AN EYE TREATED FOR CHOROIDAL MELANOMA.

PURPOSE: To report a case of a choroidal melanoma and a discrete choroidal nevus that has transformed into a malignant melanoma 5 years after initial diagnosis. METHODS: Retrospective case report. RESULTS: A diffuse macular choroidal melanoma and a discrete choroidal nevus located superonasal to the optic disk were diagnosed in the right eye of a 63-year-old woman in 2009. The patient was treated by ruthenium plaque radiotherapy for the choroidal melanoma, which consequently flattened and scarred. On a routine eye check in 2014, the nevus was found to have been transformed into a choroidal melanoma. It was treated with ruthenium plaque radiotherapy. CONCLUSION: Although extremely rare, patients with a uveal melanoma can develop an additional discrete uveal melanoma. This case highlights the importance of monitoring benign choroidal nevi in patients with a history of choroidal melanoma.

Comparison of lateral orbital decompression with and without rim repositioning in thyroid eye disease.

PURPOSE: Rim-off lateral wall decompression may be associated with functional and cosmetic deficit. Our objective, therefore, was to describe the functional and cosmetic results of deep lateral orbital decompression with and without anterior rim repositioning for thyroid eye disease. METHODS: In this retrospective comparative case series all consecutive thyroid eye disease patients who underwent deep lateral wall decompression at the Royal Victorian Eye and Ear Hospital between 1990-2007 and the Goldschleger Eye Institute, Sheba Medical Center between 2008-2011 were included. Patients were divided into two groups: the "rim-on" group in which the anterior lateral orbital rim was repositioned and the "rim-off" group in which it was left off. Main outcome measures were: proptosis reduction, postoperative oscillopsia and diplopia, presence of visible or palpable lateral orbit depression. RESULTS: One hundred and twelve patients who underwent 186 orbital decompressions were included in the final analysis. The average proptosis reduction for two- and three-wall decompressions ranged between 4.6-4.9 mm in the rim-on and 4.6-5.7 mm in the rim-off group respectively. The prevalence of postoperative oscillopsia was similar in both groups. The preoperative diplopia worsened in 17 patients (32.1 %) in the rim-on group and in seven patients (12.3 %) in the rim-off group (P = .02, chi-square test). None of the patients developed visible or palpable lateral orbit depression. CONCLUSIONS: Deep lateral orbital decompression without anterior rim repositioning may be an effective approach to enhance functional and cosmetic outcomes in thyroid eye disease patients without increasing the risk of lateral wall depression or postoperative oscillopsia.

Periocular pilomatrixoma: a retrospective analysis of 16 cases.

PURPOSE: Pilomatrixoma is a benign tumor of the hair follicle, occurring more frequently in the head and neck. There are relatively few published large case series in the ophthalmic literature. The purpose of this study was to evaluate additional case series of patients with periocular pilomatrixoma, treated in the institute from 1995 to 2011. METHODS: A retrospective analysis of all cases with periocular pilomatrixoma treated during 16 years was made. Data were collected regarding the age at the time of excision, gender, tumor location, tumor dimensions, suspected clinical diagnosis before biopsy, gross appearance, histopathological features, treatment, recurrence, and other syndromes related and family occurrence. RESULTS: Only 16 cases with pilomatrixoma were treated during 16 years. Most of the cases (69%) presented in the first 2 decades of life with female predilection (62.5%). The most common affected site was the upper eyelid (62.5%). All patients were asymptomatic. Various diagnoses were suspected clinically prior to surgical removal and histopathological confirmation of the tumor, and only in 18.75%, pilomatrixoma was suspected. Simple resection was carried out in all cases. No recurrence or malignant transformation was reported. CONCLUSION: Pilomatrixoma is a relatively infrequent periocular tumor, which isn't usually recognized clinically. The findings of the current case series, which is one of the largest published thus far in the ophthalmic literature, are in concordance with the other series of pilomatrixoma, confirming the epidemiologic, clinical, and histopathological features of this tumor in the periocular region.

Outcomes of repeated pars plana vitrectomy for persistent macular holes.

PURPOSE: To evaluate the efficacy of repeated pars plana vitrectomy with internal limiting membrane peeling and gas tamponade for persistent macular holes (MHs). METHODS: Twenty-nine eyes that underwent repeated pars plana vitrectomy and internal limiting membrane peeling for persistent MHs were included in this retrospective study. Data retrieved included demographic information, visual acuity before the first and second surgeries, MH diameter before and after both surgical procedures and throughout the follow-up, surgical details, time between surgeries, final visual acuity, and the occurrence of any complications. RESULTS: Reoperation achieved closure of the persistent MH in 68.9% of the eyes. Final visual acuity improved significantly when compared with that before the second surgery, and postoperative complications were minimal. Reoperation achieved significant improvement in visual acuity (P < 0.001), and 62% of patients gained >2 lines. The final visual acuity was significantly better in eyes with closed MH after the second surgery than that in eyes where it persisted (0.68 ± 0.37 vs. 1.17 ± 0.25 logarithm of the minimum angle of resolution, respectively, P = 0.002). Shorter interoperative time and smaller initial MH diameter were significantly correlated with better visual prognosis (P = 0.029 and 0.005, respectively). CONCLUSION: Repeated pars plana vitrectomy with internal limiting membrane peeling and gas tamponade is a safe and effective treatment option for persistent MHs. Earlier reoperation is recommended for greater visual recovery.