Faculty Bibliography

PURPOSE/OBJECTIVE:To describe recent changes in the dimensions of the ERG-jet contact lens electrode, and to suggest corresponding changes in the dimensions of cylindrical stents to facilitate the use of ERG-jet contact lens electrodes in infants and small children. METHODS:Upon the observation that existing cylindrical stents no longer fit newly purchased ERG-jet contact lenses, the spacings between the "bumps" on the front surface of old and new electrodes were measured with calipers, and prototype stents were newly machined from acrylic plastic. RESULTS:Cylindrical stents with an outside diameter of 0.277 inches (about 7.04 mm) were found to fit snugly between the front surface "bumps" of new ERG-jet contact lens electrodes. CONCLUSIONS:Recent modifications in the injection molds for ERG-jet contact lens electrodes have resulted in an increase in the space between the "bumps" on the front surface of the electrodes, necessitating a corresponding increase in the outside diameter of cylindrical stents intended to fit snugly between the "bumps" for ease of insertion and prevention of lid closure.

PURPOSE/OBJECTIVE:To evaluate the management and outcomes of naïve bilateral retinoblastoma treated at a single-center over a 5-year period during the era of ophthalmic artery chemosurgery (OAC) and intravitreous chemotherapy. METHODS:Retrospective cohort study of 46 patients (92 eyes) with naïve bilateral retinoblastoma treated at Memorial Sloan Kettering Cancer Center between January 2012 and February 2017. Indirect ophthalmoscopy, fundus photography, ultrasonography, and ultrasonic biomicroscopy were used to evaluate clinical response. Patient, ocular, ocular progression-free, ocular recurrent event-free, and second ocular survivals were assessed by Kaplan-Meier estimates. Retinal toxicity was evaluated by electroretinography. Snellen visual acuity and complete blood count metrics were recorded. RESULTS:Sixty-four eyes (70%) in 41 patients (89%) received ophthalmic artery chemosurgery as part of their treatment. Twenty-six patients (56%) received tandem OAC (bilateral simultaneous infusions). Seven eyes were primarily enucleated. No eye receiving initial OAC was enucleated. There was a single secondary enucleation in an eye initially treated with focal therapy with anterior chamber recurrence. The 3-year Kaplan-Meier estimates for overall ocular, secondary ocular (survival after treatment for recurrence), progression-free, and recurrent event-free survival were 91.3% [95% confidence interval (CI) 83.4-95.5], 98.7% (95% CI 91.3-99.8), 91.5% (95% CI 83.0-95.8), and 78.9% (95% CI 68.2-86.3), respectively. Overall and secondary ocular survivals were 100% for International Classification of Retinoblastoma (ICRB) groups A-C. Overall ocular survival was 91.5% (95% CI 70-97.8) for ICRB group D and 71.4% (95% CI 47.1-79.4) for group E. Secondary ocular survival was 95.4% (95% CI 71.8-99.3) for ICRB group D and 100% for group E. There were no treatment-related deaths, three patients developed trilateral retinoblastoma (one died), and one patient (who did not receive OAC) developed metastatic disease and is in remission at 32-month follow-up. CONCLUSION/CONCLUSIONS:The majority (89%) of bilateral retinoblastoma patients in the current era and at this center were treated with OAC. This has resulted in saving a historic number of eyes. A quarter of eyes developed recurrent disease (defined as recurrent disease requiring any treatment including focal), the majority of which occurred in the first year after treatment, and all but one was saved. There has been no compromise in patient survival.

PURPOSE/OBJECTIVE:GUCY2D has been associated with autosomal recessive Leber Congenital Amaurosis and autosomal dominant cone-rod dystrophy. This report expands the phenotype of autosomal recessive mutations to congenital night blindness which may slowly progress to retinitis pigmentosa. DESIGN/METHODS:Retrospective case series. METHODS:Multicenter study of five patients (3 male, 2 female). RESULTS:All presented with night blindness since childhood. Age at referral was 9-45 years. Length of follow up was 1-7 years. Best corrected visual acuity at presentation ranged from 20/15 to 20/30 and at most recent visit averaged 20/25. No patient had nystagmus or high refractive error. ISCEV standard electroretinography revealed non-detectable dark adapted dim flash responses, reduced amplitude but not electronegative dark adapted bright flash responses with similar waveforms to the reduced amplitude light adapted single flash responses. 30 Hz flicker responses were relatively preserved. Macular optical coherence tomography revealed normal lamination in 3, with abnormalities in 2. Goldmann visual fields were normal at presentation in children but constricted in one adult. One child showed loss of mid-peripheral fields over time. Fundus appearance was normal in childhood; the adult had sparse bone-spicule-like pigmentation. Full field stimulus testing (FST) revealed markedly decreased retinal sensitivity to light. Dark adaptation demonstrated lack of rod-cone break. 2 patients had tritanopia. All 5 had compound heterozygous mutations in GUCY2D. Three of the 5 patients harbor the Arg768Trp mutation reported in GUCY2D-associated Leber Congenital Amaurosis. CONCLUSIONS:Autosomal recessive GUCY2D mutations may cause congenital night blindness with normal acuity and refraction, and unique electroretinography. Progression to mild retinitis pigmentosa may occur.

BACKGROUND:There has been no effective method for treating newly visible ("new") subretinal seeding in retinoblastoma except enucleation. The objective of this report is to determine whether intravitreal chemotherapy combined with 810 nm indirect laser can successfully treat retinoblastoma eyes with "new" subretinal seeding which appeared after intra-arterial chemotherapy (ophthalmic arterial chemosurgery: OAC). MATERIAL AND METHODS/METHODS:Single center retrospective study from a tertiary cancer hospital of a case series of 14 eyes treated with combined intravitreal chemotherapy and laser from 2012 to 2017. Ocular salvage, patient survival, recurrence-free ocular survival, metastases, and extraocular extension were assessed. RESULTS:A total of 14 eyes in 13 unilateral or bilateral retinoblastoma patients with "new" subretinal seeding after initial eye salvage therapy were treated with combined intravitreal injection of melphalan (30 ug) or melphalan (30 ug) and topotecan (20 ug) and with 810 nm indirect continuous wave laser. All eyes were salvaged. Only two eyes (14%) recurred again for subretinal seeds after 6 and 8 months, respectively, and required additional cycles of intravitreal injections and laser. Combined intravitreal injection of melphalan or melphalan plus topotecan with 810 nm indirect continuous wave laser was not associated with any metastatic events, patient deaths, extraocular extension, or need for enucleation. CONCLUSION/CONCLUSIONS:There has been no effective treatment for "new" subretinal seeding after OAC except enucleation or second course OAC. Combined intravitreal chemotherapy with 810 nm indirect laser may be an effective and safe alternative to enucleation.

Purpose: ERGs are traditionally recorded using corneal electrodes, which can be difficult for some to tolerate. Recently, a new type of adhesive skin electrode has been introduced which may be better tolerated. We reported on the clinical usefulness of qualitative interpretation of ERG recordings using skin electrodes for a wide spectrum of retinal disorders at the 2017 ISCEV Symposium. Here we report results of a prospective quantitative comparison of simultaneous ERG recordings using contact lens and adhesive skin electrodes to compare the differences in signal strength. Methods: The study was Institutional Review Board approved. Twenty patients were enrolled by one retina specialist at the Icahn School of Medicine at Mount Sinai, referred for ERG testing for multiple clinical indications. Informed consent was obtained from patients or their accompanying parent. ERGs were obtained according to ISCEV standards. ERGs were recorded simultaneously from both eyes with ERG-jet- corneal contact lens electrodes and LKC Technologies- Sensor Strip skin electrodes using multi-channel instrumentation (Diagnosys LLC, Espion-3). A-wave and b-wave amplitudes were compared between the two electrode types. Results: Waveform morphologies obtained with skin electrodes were similar to those obtained with contact lens electrodes. The range of mean ratio of amplitudes for the right eye skin electrode to right eye contact lens electrode ranged from 0.37 to 0.54, with standard deviation (SD) from 0.19 to 0.50. The mean ratio of left eye skin electrode to left eye contact lens electrode amplitudes ranged from 0.34 to 0.42 (SD 0.16-0.40). The grand average of the response amplitude ratios between skin and contact lens electrodes for all test conditions was 0.42 (SD 0.25) for right eyes and 0.38 (SD 0.24) for left eyes. Correlations between amplitude ratios for right and left eyes ranged from 0.26 to 0.70 for the various stimulus conditions, with an overall correlation of 0.419 for all conditions combined. Conclusions: The ERGs recorded with skin electrodes had smaller amplitudes than ERGs recorded with corneal electrodes but were similar in waveform. Amplitudes obtained with skin electrodes were on average about 40% of those obtained with contact lens electrodes, but the variability of the amplitude ratio is substantial, and correlation between right and left eyes is only fair. Skin electrodes may be a useful alternative method of recording ERGs, especially in children and patients less able to tolerate traditional corneal contact lens electrode ERG testing, particularly if quantitative interpretation is not critical

Clinical electrophysiological testing of the visual system incorporates a range of noninvasive tests and provides an objective indication of function relating to different locations and cell types within the visual system. This document developed by the International Society for Clinical Electrophysiology of Vision provides an introduction to standard visual electrodiagnostic procedures in widespread use including the full-field electroretinogram (ERG), the pattern electroretinogram (pattern ERG or PERG), the multifocal electroretinogram (multifocal ERG or mfERG), the electrooculogram (EOG) and the cortical-derived visual evoked potential (VEP). The guideline outlines the basic principles of testing. Common clinical presentations and symptoms are described with illustrative examples and suggested investigation strategies.

PURPOSE:To report on the rate and timing of retinal reattachment and outcomes for retinoblastoma children who have total retinal detachments at presentation to our center and were treated with intra-arterial chemotherapy (ophthalmic artery chemosurgery, OAC). PATIENTS AND METHODS:Single-center retrospective review of retinoblastoma patients who presented with total retinal detachments and were subsequently treated with OAC at MSKCC between May 2006 and July 2016. Endpoints were retinal detachment resolution, visual function, ERG amplitude, ocular survival, and patient survival from metastases. RESULTS:87 eyes of 84 retinoblastoma patients were included. Using a survival multistate model, by 36 months of follow-up, there was a 54% cumulative probability of complete retinal reattachment and a 76% probability of partial reattachment. 24% of eyes that completely reattached received only OAC without any prior or adjuvant treatments. Eyes that completely reattached were significantly more likely to have been diagnosed at a younger age (p<0.0001) and to have greater initial ERG values (p = 0.006). At final follow-up, 14% of eyes had gained at least 25 μV of ERG activity, and 8.0% had achieved hand motion vision or better, including one to 20/60. 13% of eyes were enucleated. No patient died from metastatic disease, and only one developed metastases. CONCLUSION:OAC can successfully treat previously considered "non-salvageable" retinoblastoma eyes with total retinal detachments, promote retinal reattachment in the majority of eyes, and preserve ocular and patient survival.

PURPOSE: To compare the efficacy and toxicity of treating class 3 retinoblastoma vitreous seeds with ophthalmic artery chemosurgery (OAC) alone versus OAC with intravitreous chemotherapy. DESIGN: Retrospective cohort study. PARTICIPANTS: Forty eyes containing clouds (class 3 vitreous seeds) of 40 retinoblastoma patients (19 treated with OAC alone and 21 treated with OAC plus intravitreous and periocular chemotherapy). METHODS: Ocular survival, disease-free survival and time to regression of seeds were estimated with Kaplan-Meier estimates. Ocular toxicity was evaluated by clinical findings and electroretinography: 30-Hz flicker responses were compared at baseline and last follow-up visit. Continuous variables were compared with Student t test, and categorical variables were compared with the Fisher exact test. MAIN OUTCOME MEASURES: Ocular survival, disease-free survival, and time to regression of seeds. RESULTS: There were no disease- or treatment-related deaths and no patient demonstrated externalization of tumor or metastatic disease. There was no significant difference in the age, laterality, disease, or disease status (treatment naive vs. previously treated) between the 2 groups. The time to regression of seeds was significantly shorter for eyes treated with OAC plus intravitreous chemotherapy (5.7 months) compared with eyes treated with OAC alone (14.6 months; P < 0.001). The 18-month Kaplan-Meier estimates of disease-free survival were significantly worse for the OAC alone group: 67.1% (95% confidence interval, 40.9%-83.6%) versus 94.1% (95% confidence interval, 65%-99.1%) for the OAC plus intravitreous chemotherapy group (P = 0.05). The 36-month Kaplan-Meier estimates of ocular survival were 83.3% (95% confidence interval, 56.7%-94.3%) for the OAC alone group and 100% for the OAC plus intravitreous chemotherapy group (P = 0.16). The mean change in electroretinography responses was not significantly different between groups, decreasing by 11 muV for the OAC alone group and 22 muV for the OAC plus intravitreous chemotherapy group (P = 0.4). CONCLUSIONS: Treating vitreous seed clouds with OAC and intravitreous and periocular chemotherapy, compared with OAC alone, resulted in a shorter time to regression and was associated with fewer recurrences requiring additional treatment and fewer enucleations. The toxicity to the retina does not seem to be significantly worse in the OAC plus intravitreous chemotherapy group.