Familial retinoblastoma: variations in clinical presentation and management based on paternal versus maternal inheritance.

BACKGROUND: Several studies have demonstrated the effect of parent-of-origin on retinoblastoma penetrance. The purpose of the current study was to assess differences in clinical presentation of paternally versus maternally inherited retinoblastoma. METHODS: The clinical records of all children with familial retinoblastoma treated on a tertiary Ocular Oncology Service between December 1975 and May 2020 were reviewed retrospectively. RESULTS: A total of 179 patients with familial retinoblastoma were included. Paternal inheritance (PI) was identified in 109 (61%) patients and maternal inheritance (MI) in 70 patients (39%). A comparison (PI vs MI) revealed PI patients were older at presentation (57.2 vs 24.4 months [P = 0.002]) with no difference in patient sex (53% females vs 57% males [P = 0.606]) or number of family members affected (3.2 vs 3.0 family members [P = 0.255]). PI patients had more advanced classification according to the International Classification of Retinoblastoma (ICRB) (group E: 31% vs 8% [P = 0.012)] and greater largest tumor in basal diameter (9.0 vs 6.2 mm [P = 0.040]) and thickness (5.6 vs 4.0 mm [P = 0.038]); they were also less likely to be located in the macula (40% vs 60% [P = 0.004]). There was no difference in tumor laterality (69% vs 64% bilaterality [P = 0.530]). PI patients required enucleation more frequently (34% vs 14% [P = 0.007]). There was no difference in need for plaque radiotherapy (P = 0.86) or chemotherapy (P = 0.85). One PI patient developed metastatic retinoblastoma, and there were no retinoblastoma-related deaths. CONCLUSIONS: Patients with paternally inherited retinoblastoma presented at an older age, with larger, more peripheral tumors and more advanced ICRB group, and were more likely to require enucleation compared to those with maternally inherited retinoblastoma.

Association of Fitzpatrick Skin Type with metastatic risk from uveal melanoma in 854 consecutive patients at a single center.

OBJECTIVE: To assess the association of skin color using Fitzpatrick Skin Type (FST) with metastatic risk of uveal melanoma. SUBJECTS: 854 consecutive patients with uveal melanoma and documented FST. METHODS: Retrospective detailed review of patient charts was performed for FST (type I- white, II-fair, III-average, IV-light brown, V-brown, VI-black), clinical details of the patient and the uveal melanoma, tumor cytogenetic classification according to The Cancer Genome Atlas (TCGA), and outcome of melanoma-related metastasis and death. RESULTS: The FST classification was type I (n = 97 patients), type II (n = 665), type III (n = 79), type IV (n = 11), type V (n = 2), type VI (n = 0). A comparison of patient FST (type I vs. II vs. III-V) revealed significant differences in mean age at presentation (64.1 vs. 58.5 vs. 49.8 years, p < 0.001), race white (100% vs. 98% vs. 75%, p < 0.001), presence of ocular melanocytosis (3% vs. 3% vs. 10%, p = 0.01), visual acuity <20/200 at presentation (6% vs. 7% vs. 13%, p = 0.03), genetic results showing TCGA group B tumors (11% vs. 14% vs. 26%, p = 0.01) or TCGA group D tumors (22% vs. 11% vs. 9%, p = 0.01), 10-year incidence of melanoma-related metastasis (25% vs. 15% vs. 14%, p = 0.02) and 10-year incidence of melanoma-related death (9% vs. 3% vs. 4%, p = 0.04). FST was a significant predictor of melanoma-related metastasis (p = 0.02, Hazard ratio 2.3). CONCLUSIONS: Fitzpatrick skin type may be a predictor of melanoma-related metastasis, with metastasis and TCGA Group D tumors being more common in patients with FST I.

Effectiveness of treatment for iris melanoma: surgical versus radiotherapeutic approaches.

OBJECTIVE: To evaluate the effectiveness of preventing metastasis for each major treatment modality for iris melanoma. DESIGN: Retrospective case series. PARTICIPANTS: Three hundred consecutive eyes with iris melanoma at a single tertiary referral centre for ocular oncology. METHODS: Retrospective analysis of eyes with iris melanoma, both with (n = 69 eyes) and without (n = 231 eyes) ciliary body extension, was undertaken for metastasis-free survival at 5, 10, and 20 years based on type of treatment, including globe-sparing surgical resection (n = 169 eyes), plaque radiotherapy (n = 74 eyes), or enucleation (n = 57 eyes). RESULTS: For the total population, 5-, 10-, and 20-year metastasis-free survival rates were 95%, 93%, and 87%, respectively, and there was no difference in metastatic rates for tumours with versus without ciliary body extension (p = 0.95). Noninferiority was demonstrated for surgical resection and plaque radiotherapy, with metastasis-free survival rates of 98%, 97%, and 94% for surgical resection and 94%, 94%, and 89% for plaque radiotherapy (p = 0.002). The rates for globe salvage were 94%, 92%, and 90% for surgical resection and 94%, 86%, and 86% for plaque radiotherapy (p = 0.003). However, metastasis-free survival was worse in patients who underwent enucleation (86%, 67%, and NA; p < 0.001). CONCLUSIONS: Metastasis-free survival and globe salvage following plaque radiotherapy and surgical resection are not inferior to either, but eyes undergoing enucleation demonstrated a lower metastasis-free survival, likely because enucleation is performed for larger, more extensive melanomas, often with secondary glaucoma. In this analysis, iris melanoma with ciliary body involvement did not increase the risk of metastasis.

Timing of Jones Tube Placement After Excision of Nasal or Lacrimal Drainage System Malignancy: A Survey of the American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS).

Purpose: To elicit, from a survey of oculoplastic surgeons, the timing and reason for delaying Jones tube placement after the excision of nasal or lacrimal drainage system malignancy. Methods: The authors reviewed current literature and distributed an anonymous survey to 627 members of the American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS) to determine the length of time members wait to perform a Jones tube placement after the removal of nasal or lacrimal drainage system malignancy. The survey also included questions about the rationale for this waiting period. Results: Fifty-eight members of ASOPRS (9.3%) responded to our survey, 49 (84.4%) of whom had performed Jones tube placement on patients who had an excision of a nasal or lacrimal drainage system malignancy. Nearly 52% of respondents waited one year for Jones tube placement. However, a sizeable number of respondents opted to wait five years (15.1%). The most common rationale for waiting was a concern for tumor recurrence (42 responses). Conclusion: There is no consensus on when to perform Jones tube placement after the excision of nasal or lacrimal drainage system malignancy. This survey demonstrates a broad array of waiting periods between operations, although most surgeons wait 12 months.

Conditional Metastasis of Uveal Melanoma in 8091 Patients over Half-Century (51 Years) by Age Group: Assessing the Entire Population and the Extremes of Age.

Purpose: To evaluate cumulative incidence of metastasis at specific timepoints after treatment of uveal melanoma in a large cohort of patients and to provide comparison of conditional outcomes in the youngest and oldest cohorts (extremes of age). Methods: Retrospective analysis of 8091 consecutive patients with uveal melanoma at a single center over a 51-year period. The patients were categorized by age at presentation (0-29 years [n = 348, 4%], 30-59 years [n = 3859, 48%], 60-79 years [n = 3425, 42%], 80 to 99 years [n = 459, 6%]) and evaluated for nonconditional (from presentation date) and conditional (from specific timepoints after presentation) cumulative incidence of metastasis at five, 10, 20, and 30 years. Results: For the entire population of 8091 patients, five-year/10-year/20-year/30-year nonconditional cumulative incidence of metastasis was 15%/23%/32%/36%, and the conditional incidence improved to 6%/15%/25%/30% for patients who did not develop metastasis in the first three years. For the extremes of age (0-29 years and 80-99 years), the nonconditional cumulative incidence of metastasis revealed the younger cohort with superior outcomes at 8%/15%/19%/27% and 21%/29%/29%/29%, respectively (P < 0.001). The conditional incidence (at one-year and two-year timepoints with metastasis-free survival) showed persistent superior younger cohort survival (P < 0.001, P = 0.001), but no further benefit for patients with three-year metastasis-free survival at 4%/12%/16%/24% and 7%/18%/18%/18%, respectively (P = 0.09). Conclusions: Non-conditional metastasis-free survival analysis for patients with uveal melanoma revealed the youngest cohort to have significantly better survival than the oldest cohort, and this persisted into one-year and two-year conditional metastasis-free survival but diminished at the three-year conditional timepoint.

Intracorneal ring segment implantation in advanced Keratoconus.

PURPOSE: To compare the clinical outcomes of intracorneal ring segment (ICRS) implantation in eyes with advanced vs. mild/moderate keratoconus (KCN). METHODS: A retrospective analysis of 141 eyes of 111 patients with KCN who underwent ICRS implantation. Preoperative maximum keratometry (Kmax) was <57 diopters (D) in 70 eyes and >57 D in 71 eyes. Postoperatively, corrected distance visual acuity (CDVA), Kmax, and intraoperative and postoperative complications were assessed at 1 day, 1 month, and 1 year. RESULTS: Corneas with a preoperative Kmax >57 D experienced greater reduction in axial curvature after ICRS implantation than corneas with a preoperative Kmax <57 D (7.0 D vs. 5.5 D, p=0.005) and gained more Snellen lines of CDVA (3 vs. 1, p<0.001) by 1 year postoperatively. The incidences of the most prevalent complications (explantation, extrusion, and infectious keratitis) did not differ significantly between the two groups (p=0.29, p=0.99, p=0.98). CONCLUSIONS: The visual and topographic effects of ICRS implantation are greater in eyes with more advanced KCN, with no increase in the incidence of the most common complications.

Conjunctival Melanoma in 430 Cases: Comparative Analysis of the Impact of Orbital Invasion on Tumor Recurrence, Metastasis, and Death.

PURPOSE: To compare the clinical features at presentation and treatment outcomes of conjunctival melanoma by absence/presence of orbital invasion. METHODS: A retrospective review of patients with conjunctival melanoma managed at a single tertiary referral center from April 18, 1974, to September 9, 2019. RESULTS: Of 430 patients with conjunctival melanoma, 21 (5%) had orbital invasion at presentation. A comparison between the 2 groups (orbital invasion absent vs. present) revealed that the orbital invasion group had a higher frequency of prior eyelid incisional biopsy (5% vs. 24%, P = 0.006), greater tumor basal diameter (12.2 vs. 17.3, P = 0.009), greater tumor thickness (2.4 vs. 7.0, P < 0.001), more quadrants involved (1.8 vs. 2.5, P = 0.002), and more clock hours involved (4.4 vs. 5.8, P = 0.037). In addition, those with orbital invasion were more likely to undergo exenteration as primary treatment (1% vs. 24%, P < 0.001). Multivariate relative risk regression analysis revealed that variables predictive of orbital invasion included greater tumor thickness (P < 0.001) and greater involvement of the fornix (P = 0.031) and tarsus (P = 0.033). Outcomes revealed orbital invasion group with greater 5-year/10-year distant metastatic rate (16%/21% vs. 63%/63%, P = 0.005), and greater melanoma-related death rate (7%/13% vs. 38%/53%, P = 0.001). CONCLUSIONS: Conjunctival melanoma with orbital invasion at presentation demonstrate larger, more extensive tumors involving the fornix or tarsus, and with greater rate of melanoma-related metastasis and death.

Survey of ophthalmic imaging use to assess risk of progression of choroidal nevus to melanoma.

BACKGROUND/OBJECTIVES: The aim of this study was to ascertain the use of ocular imaging and the updated screening criteria in the evaluation of choroidal nevus across the United States. METHODS: Sixty ophthalmologists completed an anonymous 21-question survey addressing their use of the screening criteria for evaluating choroidal nevi, as well as their use of ultrasonography (US), optical coherence tomography (OCT), and autofluorescence (AF) in daily practice. RESULTS: The majority of respondents were from the Northeast (55%), worked in private practice (83%), and practiced general ophthalmology (42%). The 2009 criteria TFSOM-UHHD was used by 39 (65%) respondents, while the 2019 criteria TFSOM-DIM was used by 29 (48%) respondents. Compared to anterior segment ophthalmologists, posterior segment ophthalmologists were more likely to use the TFSOM-UHHD criteria (94% vs. 53%, OR = 13.9, p = 0.014), the TFSOM-DIM criteria (88% vs. 33%, OR = 15.5, p < 0.001), fundus AF (82% vs. 19%, OR = 20.4, p < 0.001), and US (94% vs. 42%, OR = 22.2, p = 0.004) in daily practice. CONCLUSIONS: From the survey of current practice patterns, we learned that there is a general trend of underutilization of the proper imaging modalities - and thus the criteria - in evaluating choroidal nevus. More education about ocular cancer and its screening could improve patient outcomes in the future.

Clinical outcomes of Descemet membrane endothelial keratoplasty performed in eyes with keratoconus and corneal endothelial dysfunction.

PURPOSE: To evaluate the clinical outcome of Descemet membrane endothelial keratoplasty (DMEK) performed in eyes with comorbid keratoconus (KCN) and corneal endothelial dysfunction. METHODS: Twenty-five consecutive eyes of 14 patients with comorbid stable KCN underwent DMEK for corneal endothelial dysfunction; best spectacle corrected visual acuity (BSCVA), maximum corneal curvature (Kmax), maximum corneal power (Pmax), central corneal thickness (CCT), and intra- and postoperative complications were assessed. RESULTS: Excluding eyes requiring re-transplantation for primary graft failure (n = 3), all eyes showed improvement in BSCVA, reaching ≥ 20/40 (0.5) in 86%, ≥ 20/25 (0.8) in 55%, and ≥ 20/20 (1.0) in 27% by one month postoperatively; 90%, 76%, and 48% by 6 months postoperatively; and 88%, 76%, and 47% by 12 months postoperatively. CCT decreased from 571µm preoperatively to 485µm at 1 month (p < 0.001) and 481µm at 12 months (p < 0.001). Kmax decreased by a median of 1.4 diopters (D) at 1 month (p = 0.003) and 3.1 D at 12 months (p = 0.021), and every eye with a preoperative Kmax ≥ 46 D demonstrated flattening. Pmax decreased by 2.1 D at 1 month (p = 0.001) and 4.0 D at 12 months (p = 0.016). CONCLUSION: DMEK is technically feasible in eyes with comorbid KCN and may give excellent outcomes visual and refractive outcomes, including significant corneal flattening, which may potentially create a visually significant hyperopic shift in patients with severely ectatic corneas.

Likelihood of germline mutation with solitary retinoblastoma based on tumour location at presentation.

BACKGROUND/AIMS: To evaluate the likelihood of germline mutation in patients presenting with solitary retinoblastoma based on tumour location at first examination. METHODS: Retrospective analysis of solitary unilateral retinoblastoma for likelihood of germline mutation (family history of retinoblastoma and/or genetic testing indicating germline RB1 mutation and/or development of additional new or bilateral tumours) based on tumur location at presentation (macular vs extramacular). RESULTS: Of 480 consecutive patients with solitary retinoblastoma, 85 were in the macula (18%) and 395 were extramacular (82%). By comparison (macular vs extramacular tumours), macular tumours had smaller basal diameter (12.7 mm vs 18.9 mm, p<0.001) and smaller tumour thickness (6.1 mm vs 10.7 mm, p<0.001). Patients with macular tumours demonstrated greater likelihood for germline mutation (23% vs 12%, OR=2.18, p=0.011), specifically based on family history of retinoblastoma (13% vs 2%, OR=4.64, p=0.004), genetic testing showing germline RB1 mutation (27% vs 15%, OR=2.04 (95% CI 1.04 to 4.01), p=0.039), development of new tumours (13% vs 3%, OR=5.16 (95% CI 2.06 to 12.87), p=0.001) and/or development of bilateral disease (9% vs 2%, OR=4.98 (95% CI 1.70 to 14.65), p=0.004). CONCLUSIONS: Among patients with solitary unilateral retinoblastoma, those presenting with macular tumour (compared with extramacular tumour) show 2.18 times greater likelihood for germline mutation and an even higher likelihood of development of subsequent tumours. Solitary macular retinoblastoma should raise an index of suspicion for likely germline mutation and multifocal disease.

Relationship between Fitzpatrick Skin Type and The Cancer Genome Atlas Classification with Melanoma-Related Metastasis and Death in 854 Patients at a Single Ocular Oncology Center.

BACKGROUND: The Fitzpatrick Skin Type (FST) is an objective method of classifying patients based on skin color and sunburn sensitivity. The Cancer Genome Atlas (TCGA) is a method of determining the prognosis of patients with uveal melanoma based on genetic composition of the tumor. There is no literature studying the relationship of FST and TCGA groups. MATERIALS AND METHODS: Retrospective cohort study on 854 patients with uveal melanoma treated at a single tertiary ocular oncology center between April 2006 and June 2020, classified based on FST on a scale of I-VI and based on genetic analysis with TCGA classification on a scale of A, B, C, and D. Outcome measures included uveal melanoma-related metastasis and death per FST and TCGA group. RESULTS: Patients classified as FST I (compared to FST II and III-V) had higher odds of being TCGA group D (OR 2.34, p = 0.002). Patients classified as FST III-V (compared to FST I and II) had higher odds of being TCGA group B (OR 2.26, p = 0.002). Kaplan-Meier survival analysis showed no difference in melanoma-related metastasis or death comparing FST I vs. II vs. III-V within each TCGA group at 5, 10, and 15 years. CONCLUSIONS: Patients classified as FST I are more likely to have a higher grade melanoma on genetic testing whereas those classified as FST III-V show lower grade melanoma. Despite differences in tumor features and genetic profile with various FST, survival analysis at 5, 10, and 15 years revealed no difference in melanoma-related metastasis or death within each TCGA group per skin tone.

Conditional survival of uveal melanoma using The Cancer Genome Atlas (TCGA) classification (Simplified Version) in 1001 cases.

PURPOSE: To understand conditional prognostic value of the Cancer Genome Atlas (TCGA) for uveal melanoma metastasis based on event-free survival at 1, 2, 3, 4, and 5 years. METHODS: A retrospective study of eyes with uveal melanoma categorized according to TCGA and studied for nonconditional and conditional risks for metastasis at 5 and 10 years. RESULTS: Of 1001 eyes with uveal melanoma, the nonconditional (standard, at presentation) 5-year/10-year metastatic rate was 18%/25%. The conditional 5-year/10-year metastatic rate (for those without metastasis at 2 years) revealed 10%/18% and the conditional 10-year metastatic rate (for those without metastasis at 5 years) revealed 9%. The TCGA categories included Group A (n = 486, 49%), B (n = 141, 14%), C (n = 260, 26%), and D (n = 114, 11%). The non-conditional 5-year/10-year metastatic rate revealed Group A (4%/6%), Group B (12%/20%), Group C (23%/49%), and Group D (60%/68%). The conditional 5-year/10-year metastatic rate (for those without metastasis at 2 years) revealed Group A (2%/5%), Group B (8%/18%), Group C (21%/40%), and Group D (38%/50%). The conditional 10-year metastatic rate (for those without metastasis at 5 years) revealed Group A (2%), Group B (10%), Group C (33%), and Group D (20%). The peak incidence of metastasis for Groups A and B occurred during years 5-6, C during years 4-6, and D during years 1-2. CONCLUSION: Survival outcomes for uveal melanoma as non-conditional (at presentation) and conditional (event-free survival during follow-up) reveal reduction in metastatic rate over time. For those with 5-year metastasis-free survival, the 10-year conditional risk for metastasis was 9%.

Mutational Landscape and Outcomes of Conjunctival Melanoma in 101 Patients.

PURPOSE: To evaluate targetable mutations and molecular genetic pathways in conjunctival melanoma with clinical correlation. DESIGN: Observational case series. PARTICIPANTS: Patients with conjunctival melanoma. MAIN OUTCOME MEASURES: Mutational profile of the tumor by next-generation sequencing (NGS), alternative lengthening of telomeres (ALT) by fluorescence in situ hybridization (FISH), and ATRX immunohistochemistry. Outcomes at 2 years and 5 years of tumor-related metastasis and death were recorded. RESULTS: Of the 101 patients, mean age at presentation was 60 years, 52% were male, and 88% were White. The NGS panels initially targeted BRAF only (n = 6, 6%), BRAF/NRAS (n = 17, 17%), and BRAF/NRAS/NF1 (n = 10, 10%). Sixty-eight tumors were tested with the expanded 592-gene panel. Next-generation sequencing identified high-frequency mutations in NF1 (29/74, 39%), BRAF (31/101, 31%), NRAS (25/95, 26%), and ATRX (17/68, 25%). Of those with an ATRX mutation, 12 (71%) had an additional NF1 mutation. A subset analysis of 21 melanomas showed that the ATRX mutation was associated with loss of ATRX protein expression and ALT. Loss of ATRX expression and ALT were present in both intraepithelial and invasive tumors, suggesting that an ATRX mutation is an early event in conjunctival melanoma progression. The NF1 and ATRX mutations were associated with tarsal (vs. nontarsal) tumors (NF1: 28% vs. 9%, P = 0.035, ATRX: 41% vs. 14%, P = 0.021) and orbital (vs. nonorbital) tumors (ATRX: 24% vs. 2%, P = 0.007). ATRXMUT (vs. ATRXWT) tumors were associated with a lower 2-year rate of metastasis (0% vs. 24%, P = 0.005). NRASMUT (vs. NRASWT) tumors were associated with a greater 2-year rate of metastasis (28% vs. 14%, P = 0.07) and death (16% vs. 4%, P = 0.04), with a 5-fold increased risk of death (relative risk, 5.45 [95% confidence interval, 1.11-26.71], P = 0.039). CONCLUSIONS: This study confirms the high frequency of previously documented BRAF and NRAS mutations and recently reported ATRX and NF1 mutations in conjunctival melanoma. An NRAS mutation implied increased risk for metastasis and death. Loss of ATRX and ALT may be early events in conjunctival melanoma development.

Preimplantation dehydration for corneal allogenic intrastromal ring segment implantation.

Corneal allogenic intrastromal ring segments (CAIRS) are semicircular pieces of donor corneal stroma, which may be surgically implanted to flatten keratoconic corneas. These segments can be trimmed to different thicknesses; whereas thicker segments confer greater flattening, their bulk renders them more technically challenging to insert. Consequently, thinner segments are often preferred, especially for starting surgeons. Here, we describe a technique for transiently thinning CAIRS to facilitate easy insertion, thereby permitting the use of thicker segments to achieve the maximal flattening effect.

Ten-year outcomes of uveal melanoma based on The Cancer Genome Atlas (TCGA) classification in 1001 cases.

Purpose: To understand the prognostic value of The Cancer Genome Atlas (TCGA) for uveal melanoma metastasis, using a simplified 4-category classification, based on tumor DNA. Methods: A retrospective cohort study of 1001 eyes with uveal melanoma at a single center, categorized according to TCGA as Group A, B, C, or D (by fine-needle aspiration biopsy for DNA analysis), and treated with standard methods, was studied for melanoma-related metastasis at 5 and 10 years. Results: Of 1001 eyes with uveal melanoma, the TCGA categories included Group A (n = 486, 49%), B (n = 141, 14%), C (n = 260, 26%), and D (n = 114, 11%). By comparison, increasing category (A vs. B vs. C vs. D) was associated with features of older age at presentation (56.8 vs. 52.8 vs. 61.1 vs. 63.5 years, P < 0.001), less often visual acuity of 20/20-20/50 (80% vs. 67% vs. 70% vs. 65%, P = 0.001), tumor location further from the optic disc (P < 0.001) and foveola (P < 0.001), and greater median tumor basal diameter (10.0 vs. 13.0 vs. 14.0 vs. 16.0 mm, P < 0.001) and tumor thickness (3.5 vs. 5.2 vs. 6.0 vs. 7.1 mm, P < 0.001). The Kaplan-Meier (5-year/10-year) rate of metastasis was 4%/6% for Group A, 12%/20% for Group B, 33%/49% for Group C, and 60%/not available for Group D. Conclusion: A simplified 4-category classification of uveal melanoma using TCGA, based on tumor DNA, is highly predictive of risk for metastatic disease.

Intra-arterial chemotherapy for retinoblastoma in 341 consecutive eyes (1,292 infusions): comparative analysis of outcomes based on patient age, race, and sex.

PURPOSE: To evaluate tumor control and globe salvage following intra-arterial chemotherapy (IAC) for retinoblastoma based on International Classification of Retinoblastoma (ICRB) and patient demographics. METHODS: The medical records of 313 patients (341 eyes) treated with IAC were reviewed retrospectively. Chemotherapy agents included melphalan, topotecan, and carboplatin. Comparative analysis was performed for tumor control and globe salvage based on ICRB and patient demographics including age (≤12 vs >12 months), race (white vs nonwhite), and sex. RESULTS: Of the 341 eyes treated with 1,292 consecutive infusions of IAC as primary or secondary therapy for retinoblastoma, Kaplan-Meier 5-year estimates of globe salvage was 74%. Of those treated with IAC as primary therapy (n = 160 eyes; 655 infusions), 5-year globe salvage overall was 76%: and more specifically, 100% for groups B and C, 86% for group D, and 55% for group E. Of those treated with IAC as secondary therapy (n = 207 eyes; 859 infusions), 5-year globe salvage was 71%. Comparative analysis by race and sex demonstrated no differences in outcomes, but analysis by age revealed that younger patients had a higher rate of globe salvage (77% vs 72%; P < 0.001). Complications (per catheterization) included retina ischemia (1%), choroidal ischemia (1%), neovascularization of the disk, retina, iris (NVI), glaucoma (about 1% each), and central/peripheral systemic ischemia (<1%). Younger patients showed less NVI (P = 0.028), white patients showed less retinal ischemia (P = 0.037), and no difference by sex. There were no patients with metastatic disease or death. CONCLUSIONS: Our results suggest that IAC provides substantial tumor control for advanced and/or recurrent retinoblastoma with a high rate of globe salvage and few complications. There was little difference in outcomes per age, race, and sex.

Flattening the curve: manual method for corneal allogenic intrastromal ring segment implantation.

Corneal allogenic ring segments are semicircular pieces of donor corneal stroma that may be surgically implanted to flatten keratoconic corneas. Conventionally, these donor segments are inserted into channels created using femtosecond laser dissection. However, access to femtosecond technology is not universal. In this study, an alternate, manual technique for channel creation, which is femtosecond laser independent, is described.