Qualitative and quantitative comparison of ERGs with contact lens and adhesive skin electrodes.

PURPOSE: Traditional ERGs recorded using corneal electrodes can be difficult for some patients to tolerate. In the last several years, adhesive skin electrodes have gained in acceptance. In this report we present a qualitative comparison of waveforms as well as a quantitative analysis of correlation of amplitudes and implicit times of simultaneous ERG recordings using contact lens and skin electrodes. METHODS: 89 subjects were included; all were referred for full-field ERG testing for multiple indications. ERGs (obtained according to ISCEV standards) were recorded simultaneously from both eyes with ERG-jet corneal contact lens electrodes and LKC Technologies Sensor Strip adhesive skin electrodes using multi-channel instrumentation (Diagnosys LLC, Espion3). Waveforms, a-wave and b-wave amplitudes and implicit times were compared. RESULTS: Waveform morphologies were similar between electrode types. Regression coefficients (conversion factors) for a-wave and b-wave amplitudes under both photopic and scotopic conditions were tightly clustered. Regression coefficients for implicit times were nearly equal to 1.0. The regression coefficient for the entire amplitude dataset was 0.349, with an overall correlation of 0. 869 between amplitude recorded with skin and contact lens electrodes. The regression coefficient for the entire implicit time dataset was 0.967, with an overall correlation of 0.964 between skin and contact lens electrodes. CONCLUSIONS: Our best estimate for the conversion factor between ERG amplitudes recorded with adhesive skin electrodes and contact lens electrodes is 0.349-amplitudes with skin electrodes are about 1/3 the amplitudes recorded simultaneously from the same eyes with contact lens electrodes, with a high correlation. Implicit times are nearly identical for the two electrode types.

Documentation of recovery from vitamin A deficiency-related retinopathy via multimodal imaging and electroretinogram testing.

PURPOSE: To describe vitamin A deficiency using multimodal functional visual assessments and imaging. METHODS/CASE: A 50-year-old female with past medical history significant for Roux-en-Y gastric bypass surgery complained of nyctalopia and "yellowing" of vision. RESULTS: Vitamin A levels were noted to be < 0.06 mg/L (normal 0.3-0.12 mg/L). Fundus examination was notable for peripheral yellow punctate lesions, superior arcuate defects on HVF 30-2 testing, an indistinct ellipsoid zone on SD-OCT, and absent rod responses and severely reduced amplitudes for the cone photoreceptors on full-field ERG. These findings resolved with initiation of parenteral vitamin A supplementation. CONCLUSION: This report documents an example of vitamin A deficiency in the developed world. We aim to provide a comprehensive description of clinical examination and multimodal imaging findings before and after vitamin supplementation for vitamin A deficiency.

Two cases of unilateral cone-rod dysfunction presenting in adult females.

PURPOSE: To describe cases of unilateral cone-rod dysfunction presenting in two middle-aged females. METHODS: This case series highlights two middle-aged female patients with progressive visual decline in one eye. Fundus photography, fundus autofluorescence (FAF), spectral-domain optical coherence tomography (SD-OCT), multi-focal electroretinogram (mfERG), full-field electroretinogram(ffERG), and genetic testing were obtained. RESULTS: In the first patient, mfERG showed an extinguished response and ffERG demonstrated markedly reduced a-wave and b-wave amplitudes (more pronounced under photopic conditions) in the right eye. SD-OCT showed attenuation of the ellipsoid zone of the right eye. Similar findings were appreciated in the second patient. Genetic testing in the first patient identified three heterozygous variants in PRPH2, RCBTB1, and USH2A. The second patient was found to have heterozygous variants in BBS1 and ABCA4. CONCLUSION: These two cases add to the literature of case reports of unilateral cone-rod and rod-cone dystrophies. However, the underlying etiology of the unilateral pattern of cone-rod dysfunction and the significance of the heterozygous mutations found in both cases remains uncertain.

Retinoblastoma management in 13q deletion syndrome patients using super-selective chemotherapies and other cancer-directed interventions.

BACKGROUND: This study aimed to identify best practices for treating 13q deletion syndrome (13q-) patients with retinoblastoma in the era of super-selective ophthalmic artery chemosurgery (OAC) and intravitreal injection therapy (IVIT). METHODS: Retrospective study of 21 eyes from 14 patients with retinoblastoma and 13q- who were treated at Memorial Sloan Kettering Cancer Center (MSKCC) between May 2006 and May 2020, with a mean follow up of 3.7 years. Ocular survival, patient survival, and treatment toxicities were assessed. RESULTS: Nine of the 12 eyes that underwent OAC/IVIT at MSKCC have been progression free for at least 1 year since their last treatments. Fifteen out of 26 OAC cycles resulted in grade 3-4 hematologic toxicity. There was one death from sepsis in the setting of intravenous chemotherapy (IVC) for metastatic disease that occurred after OAC/IVIT therapy. The 2-year Kaplan-Meier ocular survival estimate for the whole cohort was 75% and for the eyes that received OAC or IVIT at MSKCC 83%. For OAC hematologic toxicities, one platelet transfusion and two filgrastim doses were administered, and one patient was hospitalized for neutropenic fevers. CONCLUSIONS: The majority of 13q- eyes treated with OAC/IVIT-based regimens can be cured, and there were no deaths related to complications from OAC or IVIT. 13q- Patients did have increased risk of systemic treatment complications, even from super-selective chemotherapies. Despite these toxicities, only one patient developed febrile neutropenia, one patient required a blood product transfusion, and two patients received filgrastim for both OAC and IVC complications. PRÉCIS: Children with 13q deletion syndrome with retinoblastoma managed with intra-arterial and intravitreal chemotherapy have excellent patient and ocular survival with acceptable toxicity.

TOXICITY AND EFFICACY OF INTRAVITREAL MELPHALAN FOR RETINOBLASTOMA: 25 µg Versus 30 µg.

PURPOSE: To compare retinal toxicity as measured by electroretinogram, ocular, and patient survival in retinoblastoma treated with intravitreal melphalan at two concentrations (25 vs. 30 µg). METHODS: Single-center, retrospective analysis of retinoblastoma eyes receiving 25-µg or 30-µg intravitreal melphalan from September 2012 to January 2019. Ocular toxicity was measured by electroretinogram of evaluable injections in 449 injections in 136 eyes. A repeated-measures linear mixed model with a random intercept and slope was applied to account for repeated measures for each eye. RESULTS: Average decline in electroretinogram after each additional injection was -4.9 µV (95% confidence interval -6.3 to -3.4); electroretinogram declined by -4.6 µV (95% confidence interval -7.0 to -2.2) after 25-µg injections and -5.2 µV (95% confidence interval -6.6 to -3.8) after 30-µg injections (P = 0.66). Injection at a new clock site hour was associated with a -3.91-µV lower average (95% confidence interval -7.8 to -0.04). CONCLUSION: Electroretinogram-measured toxicity in retinoblastoma eyes treated with intravitreal injections was not found to be different across 25-µg and 30-µg injections. There were no cases of extraocular extension or metastatic deaths in our patient population.

Oscillatory potentials in patients with birdshot chorioretinopathy.

PURPOSE: The electroretinogram (ERG) has proven to be useful in the evaluation and monitoring of patients with posterior uveitis. ERG oscillatory potentials (OPs) are sometimes reduced in many uveitic eyes with otherwise grossly normal ERG responses. This study compares ERG parameters, including OPs, between patients with birdshot chorioretinopathy, other posterior uveitis, and controls. METHODS: This was a retrospective case-control study. Sixty-four patients seen at a clinical practice had a total of 93 visits during which ERG was performed on both eyes. ERG data from 93 age-matched controls were also collected. Root-mean-squared (RMS) energy of the OPs was calculated using Fourier analysis for 88 patients and 88 age-matched controls for whom complete data were available. Photopic flicker amplitudes, photopic flicker latencies, scotopic b-wave amplitudes, and OP RMS values were compared between patients and controls. Diagnostic performance was assessed using receiver operating characteristic (ROC) curves. RESULTS: The mean ages of patients and controls were 55.9 ± 10.8 (SD) years and 55.1 ± 11.5, respectively. 83% of the patients had a diagnosis of BCR. The mean OP RMS value was significantly different in patients (15.6 µV ± 9.7 µV) versus control eyes (33.0 µV ± 12.7 µV), p < 0.001. Area under the ROC curves (AUROC) was 0.75 for photopic flicker amplitudes, 0.77 for photopic flicker latencies, 0.72 for scotopic b-wave amplitudes, and 0.88 for OP RMS. AUROC was significantly different between OP RMS and photopic flicker amplitudes (p < 0.001), between OP RMS and flicker latencies (p = 0.0032), and between OP RMS and scotopic b-wave amplitudes (p < 0.0001). CONCLUSION: Analysis of OPs shows greater sensitivity and specificity in the diagnosis and evaluation of patients with birdshot chorioretinopathy than photopic and scotopic ERG amplitudes and photopic flicker latencies.

Modified ERG-Jet™ contact lens electrodes for use in infants and toddlers-update.

PURPOSE: 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.

ISCEV guide to visual electrodiagnostic procedures.

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.

Retinoblastoma Vitreous Seed Clouds (Class 3): A Comparison of Treatment with Ophthalmic Artery Chemosurgery with or without Intravitreous and Periocular Chemotherapy.

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 naïve 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 µV for the OAC alone group and 22 µV 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.

Efficacy and Toxicity of Intravitreous Chemotherapy for Retinoblastoma: Four-Year Experience.

PURPOSE: To investigate the efficacy and toxicity of intravitreous melphalan for treatment of retinoblastoma, as a single agent or with concomitant topotecan. PARTICIPANTS: A total of 130 eyes of 120 patients with retinoblastoma receiving 630 intravitreous (melphalan, topotecan) or topotecan periocular injections. A total of 83 (64%) of these eyes were treated with concomitant ophthalmic artery chemosurgery (OAC). DESIGN: Retrospective cohort study. METHODS: Indirect ophthalmoscopy and clinical imaging were used to evaluate clinical response. Ocular survival and disease-free survival were estimated using Kaplan-Meier methods in 130 eyes. Ocular toxicity was evaluated by clinical findings and electroretinography (ERG) on 244 evaluable injections in 63 patients using 30-Hz flicker responses. Analysis was performed using linear mixed effects models with a random intercept and slope for each patient and a fixed effect for number of injections, in addition to any other fixed effect of interest. MAIN OUTCOME MEASURES: Ocular survival, disease-free survival, ERG: peak-to-peak ERG amplitudes in response to 30-Hz photopic flicker stimulation. RESULTS: There were no disease- or treatment-related deaths, and no patient developed externalization of tumor or metastatic disease. Two-year Kaplan-Meier estimates of ocular survival and disease-free survival were 94.2% (95% confidence interval, 89.2-99.4) and 86.2% (95% confidence interval, 78.7-94.5), respectively. There was a significant association between the number of injections and diminished ERG responses, such that on average each intravitreous melphalan injection was associated with a 5.3-µV decrease in ERG amplitude (P < 0.001). Concomitant intra-arterial chemotherapy (P = 0.01) and greater inherent ocular pigment also were significantly associated with a reduction in ERG (P = 0.045). Patient age and weight, new injection site location, addition of topotecan, concomitant focal treatment, and time interval between injections were not significantly associated with toxicity. CONCLUSIONS: Intravitreous melphalan is an effective treatment for vitreous seeding in retinoblastoma, resulting in high rates of ocular survival and disease-free survival. However, in this study, each injection of melphalan was associated, on average, with a decrement in ERG response. The findings suggest increased toxicity (1) when OAC is given within 1 week of the intravitreous injection and (2) in more deeply pigmented eyes.

Efficacy and toxicity of second-course ophthalmic artery chemosurgery for retinoblastoma.

OBJECTIVE: Assess the usefulness of second-course ophthalmic artery chemosurgery (OAC) for patients with intraocular retinoblastoma that recurred after prior OAC. This study evaluated the efficacy and toxicity of second-course OAC. DESIGN: Single-arm retrospective study of 29 eyes of 30 patients treated with second-course OAC at Memorial Sloan Kettering Cancer Center between May 2006 and July 2013, with a median follow-up of 25.9 months. PARTICIPANTS: Retinoblastoma patients who underwent a course of OAC, with a minimum of 2 months of progression-free follow-up at monthly examinations, but who subsequently received additional OAC for recurrent tumor. METHODS: To determine efficacy, Kaplan-Meier survival estimates were generated and the Mantel-Cox test was used to compare curves. To determine toxicity, electroretinography (ERG) amplitudes were measured in response to 30-Hz photopic flicker stimulation before and after OAC treatment; systemic adverse events were graded according to the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE 4.0). MAIN OUTCOME MEASURES: For efficacy, ocular progression-free survival, ocular event-free survival (e.g., enucleation, external-beam radiation, or intravitreal melphalan), and ocular survival. For toxicity, peak-to-peak comparisons between ERG studies before and after OAC treatment and CTCAE 4.0-graded systemic adverse events. RESULTS: Fifty percent of all recurrences were within 4.4 months and 90% were within 16 months of completion of the first course of OAC. The 2-year Kaplan-Meier ocular survival, event-free survival, and progression-free survival estimates after second-course OAC were 82.8% (95% confidence interval [CI], 60.1%-93.2%), 57.3% (95% CI, 36.1%-73.7%), and 26.5% (95% CI, 11.0%-45.0%), respectively. All eyes without vitreous seeding were progression free, whereas eyes with vitreous seeding were associated significantly with worse ocular survival after second-course OAC (P = 0.03). After second-course OAC, 90% of eyes had stable or improved ERG responses. Of all evaluable cases, there was no increased risk of systemic toxicity during the second course compared with the initial course of OAC. CONCLUSIONS: Retinoblastoma eyes requiring second-course OAC after initial OAC treatment have good salvage rates, and the treatment has an acceptable ocular and systemic toxicity profile. However, these eyes often require additional (third- or fourth-course) OAC or other treatment methods because of progression of disease after second-line OAC, particularly if vitreous seeds are present at the time of initial OAC failure.

Local and systemic toxicity of intravitreal melphalan for vitreous seeding in retinoblastoma: a preclinical and clinical study.

PURPOSE: Intravitreal melphalan is emerging as an effective treatment for refractory vitreous seeds in retinoblastoma, but there is limited understanding regarding its toxicity. This study evaluates the retinal and systemic toxicity of intravitreal melphalan in retinoblastoma patients, with preclinical validation in a rabbit model. DESIGN: Clinical and preclinical, prospective, cohort study. PARTICIPANTS: In the clinical study, 16 patient eyes received 107 intravitreal injections of 30 µg melphalan given weekly, a median of 6.5 times (range, 5-8). In the animal study, 12 New Zealand/Dutch Belt pigmented rabbits were given 3 weekly injections of 15 µg of intravitreal melphalan or vehicle to the right eye. METHODS: Electroretinogram (ERG) responses were recorded in both humans and rabbits. For the clinical study, ERG responses were recorded at baseline, immediately before each injection, and at each follow-up visit; 82 of these studies were deemed evaluable. Median follow-up time was 5.2 months (range, 1-11). Complete blood counts (CBCs) were obtained on the day of injection at 46 patient visits. In the animal study, ERG responses were obtained along with fluorescein angiography, CBCs, and melphalan plasma concentration. After humane killing, the histopathology of the eyes was evaluated. MAIN OUTCOME MEASURES: For the clinical study, we measured peak-to-peak ERG amplitudes in response to 30-Hz photopic flicker stimulation with comparisons between ERG studies before and after intravitreal melphalan. For the animal study, we collected ERG parameters before and after intravitreal melphalan injections with histopathologic findings. RESULTS: By linear regression analysis, over the course of weekly intravitreal injections in retinoblastoma patients, for every additional injection, the ERG amplitude decreased by approximately 5.8 µV. The ERG remained stable once the treatment course was completed. In retinoblastoma patients, there were no grade 3 or 4 hematologic events. One week after the second injection in rabbits, the a- and b-wave amplitude declined significantly in the melphalan treated eyes compared with vehicle-treated eyes (P<0.05). Histopathology revealed severely atrophic retina. CONCLUSIONS: Weekly injections of 30 µg of melphalan can result in a decreased ERG response, which is indicative of retinal toxicity. These findings are confirmed at an equivalent dose in rabbit eyes by ERG measurements and by histopathologic evidence of severe retinal damage. Systemic toxicity with intravitreal melphalan at these doses in humans or rabbits was not detected.

Tips and tricks for successful electroretinography in children.

PURPOSE OF REVIEW: The role of electroretinography in pediatric practice, and to offer suggestions for successful electroretinography recordings in children. RECENT FINDINGS: Electroretinography can be usually be obtained in infants without resorting to general anesthesia. When general anesthesia is required, modifications to standard protocols can often reduce total anesthesia time without compromising the clinical value of the study. SUMMARY: With appropriate technique, electroretinography methods could be made more widely available for pediatric diagnosis.

Non-selectivity of ERG reductions in eyes treated for retinoblastoma.

PURPOSE: We have monitored retinal function in patients treated for retinoblastoma (primarily, but not exclusively by intra-arterial chemotherapy infusion) by electroretinography (ERG) recordings for the past 7 years. We here present data from 599 ERG studies of 108 patients, in which a complete ERG protocol including both photopic and scotopic recordings was performed, in justification of our frequent practice of reporting primarily 30-Hz photopic flicker amplitude data. METHODS: Patients referred for treatment of retinoblastoma underwent ERG recordings during examination under anesthesia whenever possible: at baseline and following most treatment sessions. Correlations were calculated for the complete datasets between the four primary amplitude response parameters: photopic single flash b-wave, photopic 30-Hz flicker peak-to-trough, scotopic rod-isolating b-wave, and scotopic maximal flash b-wave. RESULTS: Using our adaptation of the International Society for Clinical Electrophysiology of Vision-recommended standard ERG protocol, ERG responses of eyes of patients with untreated retinoblastoma or following traditional or intra-arterial treatment for retinoblastoma show very high correlations between 30-Hz flicker amplitude responses and three other standard photopic and scotopic ERG response amplitudes. Reductions in ERG amplitudes seen in these eyes following treatment show no significant difference between retinal dysfunction estimated using rod- or cone-dominated responses. CONCLUSION: These observations support the use of photopic response amplitudes (especially in response to 30-Hz flicker) as the primary ERG outcome measure in studies of treated and untreated eyes with retinoblastoma when more complete ERG protocols may be impractical.

Retinal toxicities of cancer therapy drugs: biologics, small molecule inhibitors, and chemotherapies.

PURPOSE: To review reported retinal side effects from current cancer therapy drugs. METHODS: Retinal toxicities from ophthalmologic or oncologic case reports, case series, and clinical trials were identified by a systematic literature search using Lexicomp and PubMed. RESULTS: Four biologics, 8 small molecule inhibitors, and 17 traditional chemotherapy agents had reported retinal side effects. For biologics, interferon alpha 2b was associated with retinopathy, denileukin diftitiox with pigmentary retinopathy, ipilimumab with a Vogt-Koyanagi-Harada-like syndrome, and trastuzumab with retinal ischemia. For small molecule inhibitors, v-raf murine sarcoma viral oncogene homolog B (BRAF) inhibitors were associated with uveitis, mitogen-activated protein kinase/extracellular signal-regulated kinase inhibitors with pigment epithelium detachments, and tyrosine kinase inhibitors with macular edema. Steroid antagonists were associated with crystalline retinopathy and macular edema. Nitrosoureas, platinum analogs, and cytosine arabinoside were associated with retinal vascular occlusions. Antimicrotubular agents were associated with cystoid macular edema but without fluorescein leakage. Retinoic acid derivatives were associated with impaired night vision, and mitotane was associated with a pigmentary retinopathy and papilledema. CONCLUSION: Certain agents used in the treatment of systemic cancer are associated with ocular complications. Awareness of these complications will allow early detections and maybe reversal of some of the ocular problems.

Ophthalmic findings in the KIF1A-associated neurological disorder (KAND).

PURPOSE: To define the ophthalmic manifestations in KIF1A-associated neurological disorder (KAND), a rare, progressive neurodegenerative disorder caused by pathogenic variants in the KIFA1 gene. DESIGN: Cross-sectional study. METHODS: Clinical ophthalmic examination and multimodal imaging were performed for 24 participants enrolled in the KIF1AOutcome measures, Assessments, Longitudinal And endpoints (KOALA) Study. Visual evoked potentials (VEP) were performed on select participants. RESULTS: The average central visual acuity in pediatric participants was 20/43 (logMAR 0.329, range 0.0-1.0), and 20/119 (logMAR 0.773, range 0.471-1.351) in adults. Ninety-five percent of participants examined had some degree of optic nerve atrophy detected by clinical examination and/or optical coherence tomography (OCT). Almost forty percent had strabismus. Color vision, visual fields and stereopsis were impaired in most participants who were able to participate in testing. VEP showed varying degrees of signal slowing and diffuseness. CONCLUSIONS: Optic nerve atrophy is the primary ocular finding in individuals with KAND and is present at higher prevalence than previously reported. The degree of the atrophy is likely dependent on the severity of the pathogenic variant and possibly the age of the patient. Adults had worse vision on average than children, suggesting possible decline in vision with age. Strabismus in this cohort was common. Visual evoked potentials showed findings consistent with optic neuropathy and visual dysfunction even in the absence of obvious structural changes on OCT. Families should be counseled regarding visual impairment in KAND patients, so as to obtain appropriate support and assistance to maximize safety, functionality, and learning.

Ophthalmic artery chemosurgery for retinoblastoma prevents new intraocular tumors.

OBJECTIVE: To determine the incidence and timing of new intraocular tumor foci in genetic retinoblastoma cases after treatment with ophthalmic artery chemosurgery (OAC). DESIGN: Single-center retrospective review of all genetic retinoblastoma cases managed at Memorial Sloan-Kettering Cancer Center/Weil-Cornell Medical School since May 2006. PARTICIPANTS: Eighty-one patients (80 with bilateral disease and 1 with unilateral disease with a family history) with genetic retinoblastoma, with a total of 116 eyes treated with OAC since May 2006. METHODS: Retrospective, single-institution review of patients with bilateral retinoblastoma and unilateral retinoblastoma with a positive family history. New tumors were assessed by clinical notes, retinal drawings, and RetCam digital imaging (Clarity Medical Systems, Pleasanton, CA). MAIN OUTCOME MEASURES: New intraocular retinoblastoma tumors after treatment with OAC. RESULTS: Forty-one eyes were treated primarily with OAC (treatment-naïve group) and 75 eyes were treated with OAC after prior treatment with systemic chemotherapy, external beam radiation, or both and focal techniques. Of the 41 treatment-naïve eyes, a new intraocular tumor (one focus) subsequently developed in 1 eye. Of the 75 previously treated eyes, new tumors (single focus in each eye) subsequently developed in 6 eyes. CONCLUSIONS: Eyes receiving OAC demonstrate fewer new intraocular retinoblastomas after radiation or systemic chemotherapy than has been reported in the literature. This suggests that ophthalmoscopically undetectable tumors are present at the initial diagnosis and effectively are eliminated as a result of OAC.

Ocular manipulation reduces both ipsilateral and contralateral electroretinograms.

PURPOSE: To determine the electroretinogram (ERG) changes in eyes manipulated in the course of local ablative therapy (transpupil thermotherapy (TTT), cryotherapy or both) or scleral depression and in un-manipulated fellow, healthy eyes. METHODS: This prospective observational report summarizes 73 ERG studies in 42 patients with retinoblastoma; a study consisted of ERGs of one or both eyes (if present) followed by ocular manipulation (scleral depression, cryotherapy, transpupillary thermotherapy, pressure applied to orbital implant in an anophthalmic socket, or a 5- or 10-min delay without mechanical manipulation) followed by a repeat of the ERGs. Each patient was studied with only a single manipulation modality on any given date: 23 patients were studied only once, and 19 patients were included in more than one study occasion. RESULTS: Following local ablative treatment of patients with unilateral retinoblastoma, the photopic response decreased significantly in both the treated eye and the untouched fellow, healthy eye. Following scleral depression of the diseased eye, the photopic response immediately decreased in the diseased eye by a mean of 16 µV (21 %, p = .006) and, in the fellow, healthy eye by 40 µV (23 %, p = .0005). Following scleral depression of the fellow, healthy eye, the photopic response immediately decreased by a mean of 11 µV (4 %, p = .37) in the fellow, healthy eye, and by 16 µV (28 %, p = .01) in the diseased eye. CONCLUSIONS: Following physical ocular manipulation, the amplitude of the photopic response decreased in the manipulated, but also the untouched healthy, fellow eyes. These findings may account for some of the variation in clinical ERG recordings, particularly that observed following ocular manipulation by TTT, laser or even scleral depression.