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

IMPORTANCE Demonstrating the usefulness and complications of multiagent intravitreal chemotherapy is necessary for successful treatment in patients with recalcitrant vitreous seeding of retinoblastoma.OBJECTIVE To determine the efficacy and complications of combined intravitreal chemotherapy (melphalan hydrochloride and topotecan hydrochloride) for viable vitreous seeding from retinoblastoma. DESIGN, SETTING, AND PARTICIPANTS This retrospective study was conducted in a hospital setting. Trans-pars plana intravitreal injection of melphalan hydrochloride (40 μg in 0.04 mL of diluent) combined with topotecan hydrochloride (8-20 μg in 0.04 mL of balanced salt solution) was performed in 9 eyes, followed by injection site cryotherapy. MAIN OUTCOMES AND MEASURES Complete regression of vitreous seeds of retinoblastoma.RESULTS Nine eyes, initially classified as group D (n = 6) or E (n = 3) according to International Classification of Retinoblastoma categorization, received a standard 6 cycles of intravenous chemotherapy and/or intra-arterial chemotherapy and subsequently developed recurrent viable vitreous seeds. Intravitreal administration of melphalan combined with topotecan produced complete control of vitreous seeds in all 9 eyes following a mean of 1.9 injections (median, 2; range, 1-3 injections). In 3 cases (33%), tumor control was achieved with a single injection, whereas in 6 (67%) cases, 2 or 3 injections were necessary. Three patients (33%) subsequently underwent enucleation because of recurrent tumor and persistent anterior chamber lesions. During a mean 15.2 months of follow-up (median, 16; range, 7-25 months), there was no recurrence of new tumor or vitreous seeds in the remaining 6 eyes. Complications included temporary hypotonia of 2 weeks or less (2 [22%]), temporary epithelial defect (1 [11%]), and vitreous hemorrhage (1 [11%]). There was no case of episcleral or orbital retinoblastoma extension or remote retinoblastoma metastasis. There was no change in the a and b waves of bright-flash electroretinograms.CONCLUSIONS AND RELEVANCE Administration of combined intravitreal melphalan and topotecan in eyes not subsequently enucleated appears to be safe and effective for resistant or recurrent vitreous seeds from retinoblastoma. In 3 of the cases (33%), tumor control was achieved with a single injection.

Intrastromal injection of voriconazole together with topical voriconazole effectively reduced the infiltration size and controlled the infection in patients with Fusarium keratitis. However, continued application of the topical medication is critical for a favorable outcome of treatment.

Recurrence of neovascularization with bevacizumab monotherapy seems to be higher than that with conventional laser therapy among infants with Type 1 ROP in zone II ROP but reinjection of bevacizumab causes regression in most recurrent cases.

Purpose: To evaluate and compare three different techniques of inverted internal limiting membrane (ILM) flap in the treatment of large idiopathic full-thickness macular hole. Methods: In a comparative interventional case series, 72 eyes from 72 patients with large (> 400 µm) full-thickness macular hole were randomly enrolled into three different groups: group Ahemicircular ILM peel with temporally hinged inverted flap; group Bcircular ILM peel with temporally hinged inverted flap; and group Ccircular ILM peel with superior inverted flap. Best-corrected visual acuity (BCVA), anatomical closure rate, and ellipsoid zone (EZ) or external limiting membrane (ELM) defects were evaluated preoperatively, at week 1, and months 1, 3 and 6 after surgery. Results: There were 24 eyes in group A, 23 in group B, and 25 in group C. In all three groups, larger diameter macular hole was associated with worse preoperative visual acuity (r=0.625, P<0.001). Mean BCVA improved significantly in all three groups 6 months after surgery (0.91vs 0.55, p<0.001). 6 months after surgery, mean BCVA improved from 0.91 logMAR to 0.52±0.06 in group A, 0.90 to 0.53±0.06 in group B, and 0.91 to 0.55±0.11 in group C. In group A vs. B vs. C, improvement of BCVA was 0.380±0.04 vs. 0.383±0.04 vs. 0.368±0.11 logMAR, with no statistically significant difference between groups (P=0.660). The rate of successful hole closure was 87.5% vs. 91.3% vs. 100%. Although the closure rate was 100% in Group C (circular ILM peel with superiorly hinged inverted flap), this difference was not statistically significant (P=0.115). Conclusion: ILM peel with an inverted flap is a highly effective procedure for the treatment of large, full-thickness macular hole. Different flap techniques have comparable results, indicating that the technique can be chosen based on surgeon preference.

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This manuscript focuses on high-risk factors of metastatic disease in retinoblastoma and evaluation of the current treatments of retinoblastoma. Presence of histopathologic high-risk factors is associated with a higher risk of local recurrence and systemic metastasis. Currently, globe-sparing therapies, including systemic chemotherapy, intra-arterial chemoreduction, intravitreal chemotherapy, focal consolidation, and combination therapies, are being used and investigated actively. Major advances are being made in the diagnosis and management of retinoblastoma that will lead to improved morbidity and mortality rates in patients with retinoblastoma. By saving the globes, fronting with some high-risk factors for metastasis would be inevitable. International multi-institutional prospective studies could resolve current uncertainties regarding the main tumor treatment regimens for each patient and indications for chemoprophylaxis for high-risk-factor-bearing retinoblastoma cases.

PurposeTo characterize the optic nerve head (ONH) structure in patients with non-arteritic anterior ischemic optic neuropathy (NAION) compared to healthy control subjects using spectral domain optical coherence tomography (SD-OCT) via the enhanced depth imaging method.MethodsIn this prospective, cross-sectional, comparative study, we assessed 66 eyes of 33 patients with unilateral NAION and 31 eyes of 31 healthy normal subjects in an academic institution. The peripapillary nerve fiber layer thickness, disc area, and quantitative parameters of the ONH structures, including the Bruch's membrane opening (BMO) area, anterior laminar depth, and prelaminar thickness and depth were compared between the three groups.ResultsLinear mixed model analysis after adjusting for age, sex, and axial length showed that the BMO area was similar in eyes with NAION (1.89±0.33 mm), their fellow eyes (1.85±0.35 mm), and control eyes (1.88±0.37 mm; all P>0.99). Anterior laminar depth was also similar in the three groups. The mean prelaminar tissue thickness of the NAION eyes was 445±176 μm, which was thinner than the prelaminar tissue of their unaffected fellow eyes (mean, 539±227 μm, P=0.004), but both were thicker than the prelaminar tissue of the normal subjects (mean 243±145 μm, P=0.001 and P<0.001, respectively).ConclusionsThe thick prelaminar thickness is associated with unilateral NAION in the affected and unaffected eyes.