A Review of Pediatric Ophthalmic Tumors.

Tumors of the eye, orbit, and ocular adnexa can arise in the pediatric population. These entities can be both vision- and life-threatening and may be associated with systemic disease. Given their relative rarity, pediatricians must be aware of these conditions and understand what findings warrant immediate referral to an ophthalmologist for initiation of further testing. We aimed to review these conditions and highlight clinical features to promote awareness and expedite diagnosis. Tumors are subdivided into the following categories for review: anterior tumors of the eyelid and ocular surface, orbital tumors, and intraocular tumors.

Ophthalmologic Findings in Pediatric Erdheim-Chester Disease: A Literature Review With a Novel Case Report.

PURPOSE: The authors aim to describe the ophthalmologic manifestations of pediatric Erdheim-Chester disease (ECD). METHODS: The authors describe a novel case of ECD presenting as isolated bilateral proptosis in a child and provide a comprehensive review of the documented pediatric cases to observe overall trends and ophthalmic manifestations of disease. Twenty pediatric cases were identified in the literature. RESULTS: The mean age at presentation was 9.6 years (1.8-17 years) with a mean time of symptom presentation to diagnosis of 1.6 years (0-6 years). Nine patients (45%) had ophthalmic involvement at diagnosis, 4 who presented with ophthalmic complaints: 3 with observable proptosis and 1 with diplopia. Other ophthalmic abnormalities included eyelid findings of a maculopapular rash with central atrophy on the eyelids and bilateral xanthelasmas, neuro-ophthalmologic findings of a right hemifacial palsy accompanied by bilateral optic atrophy and diplopia, and imaging findings of orbital bone and enhancing chiasmal lesions. No intraocular involvement was described, and visual acuity was not reported in most cases. CONCLUSIONS: Ophthalmic involvement occurs in almost half of documented pediatric cases. Typically presenting with other symptoms, the case highlights that isolated exophthalmos may be the only clinical sign, and ECD should be included in the differential diagnosis of bilateral exophthalmos in children. Ophthalmologists may be the first to evaluate these patients, and a high index of suspicion and an understanding of the varied clinical, radiographic, pathologic, and molecular findings are critical for prompt diagnosis and treatment of this unusual disease.

Targeted Neoadjuvant Intra-arterial Chemotherapy in Lacrimal Gland Adenoid Cystic Carcinoma: A Histological Correlation Using Apoptotic Tumor Markers.

Neoadjuvant intra-arterial cytoreductive chemotherapy is used for the treatment of lacrimal gland adenoid cystic carcinomas (ACC) to improve outcomes in this condition with an otherwise dismal prognosis. We share our experience in the management of an advanced case of ACC using a novel, highly targeted intra-arterial cytoreductive chemotherapy delivery technique involving both the internal and external carotid circulation, with an attempt to correlate the effect histologically. Refinement of the chemotherapy delivery using the tumor's vascular anatomy and appropriate blood vessel selection may lead to future globe sparing procedures without compromising survival.

Response criteria for intraocular retinoblastoma: RB-RECIST.

Standardized guidelines for assessing tumor response to therapy are essential for designing and conducting clinical trials. The Response Evaluation Criteria In Solid Tumors (RECIST) provide radiological standards for assessment of solid tumors. However, no such guidelines exist for the evaluation of intraocular cancer, and ocular oncology clinical trials have largely relied on indirect measures of therapeutic response-such as progression-free survival-to evaluate the efficacy of treatment agents. Herein, we propose specific criteria for evaluating treatment response of retinoblastoma, the most common pediatric intraocular cancer, and emphasize a multimodal imaging approach for comprehensive assessment of retinoblastoma tumors in clinical trials.

A Potential Role For Apparent Diffusion Coefficient in the Diagnosis of Trilateral Retinoblastoma.

We attempted to investigate the potential role for apparent diffusion coefficient (ADC) to diagnose trilateral retinoblastoma (TRb) by retrospectively reviewing brain magnetic resonance images of retinoblastoma patients. Observations: The median ADC measured 620.95 for TRb (n=6) and 1238.5 for normal pineal gland in bilateral retinoblastoma (n=8). Monitoring ADC trends aided in establishing the appropriate diagnoses in 3 patients (2 TRb, 1 benign pineal cyst). Conclusions: Our results provide baseline reference data and describe the importance of downward trending ADC which should prompt consideration of TRb. Unchanged high/nonrestricted values (>1000) may distinguish those with benign pineal tissue and obviate invasive neurosurgical procedures.

A case of bilateral acute depigmentation of the Iris in one of two identical twins.

BACKGROUND: Bilateral Acute Depigmentation of the Iris (BADI) is a condition which was first described in a case series from Turkey by Tugal-Tutkin and Urgancioglu in (Graefes Arch Clin Exp Ophthalmol 244:742-6, 2006). The condition is characterized by bilateral acute depigmentation and discoloration of the iris stroma, pigment dispersion, and deposition of pigment in the angle. In our case we report a patient who developed BADI after receiving pitcher plant extract injections for chronic migraine, while her identical twin sister has normal iris architecture and pigmentation and never received any pitcher plant injections. CASE PRESENTATION: Patient is a 41-year-old female with history of pitcher plant extract injections to her face for chronic migraine, who later developed bilateral depigmentation of the iris. She did not have any signs of anterior segment uveitis or iridocyclitis. She has an identical twin sister who maintained normal iris pigmentation during the entire course. CONCLUSIONS: Bilateral Acute depigmentation of the is a recently discovered condition described in the literature in Turkish patients (Tugal-Tutkun and Urgancioglu, Graefes Arch Clin Exp Ophthalmol 244:742-6, 2006; Tugal-Tutkun et al., Ophthalmology 116(8):1552-7, 2009). This condition affects mainly young females and is characterized by acute bilateral stromal depigmentation, without other pathologic ocular findings. These patients usually maintain normal vision and do not develop significant glaucoma from pigment collecting in the anterior chamber angle. This condition can be mistaken for Fuchs' heterochromic iridocyclitis, pigment dispersion syndrome, pseudoexfoliation syndrome, and viral iridocyclitis. This is the first reported case in North America and is important for differentiation from the above pathologies. Our patient had a history of pitcher plant extract injections to the face but it is unclear if this is associated with our patient's development of BADI. As awareness of this condition progresses, a possible etiology may be elucidated.

Screening Children at Risk for Retinoblastoma: Consensus Report from the American Association of Ophthalmic Oncologists and Pathologists.

PURPOSE: To provide a set of surveillance guidelines for children at risk for development of retinoblastoma. DESIGN: Consensus panel. PARTICIPANTS: Expert panel of ophthalmic oncologists, pathologists, and geneticists. METHODS: A group of members of the American Association of Ophthalmic Oncologists and Pathologists (AAOOP) with support of the American Association for Pediatric Ophthalmology and Strabismus and the American Academy of Pediatrics (AAP) was convened. The panel included representative ophthalmic oncologists, pathologists, and geneticists from retinoblastoma referral centers located in various geographic regions who met and discussed screening approaches for retinoblastoma. A patient "at risk" was defined as a person with a family history of retinoblastoma in a parent, sibling, or first- or second-degree relative. MAIN OUTCOME MEASURES: Screening recommendations for children at risk for retinoblastoma. RESULTS: Consensus statement from the panel: (1) Dedicated ophthalmic screening is recommended for all children at risk for retinoblastoma above the population risk. (2) Frequency of examinations is adjusted on the basis of expected risk for RB1 mutation. (3) Genetic counseling and testing clarify the risk for retinoblastoma in children with a family history of the disease. (4) Examination schedules are stratified on the basis of high-, intermediate-, and low-risk children. (5) Children at high risk for retinoblastoma require more frequent screening, which may preferentially be examinations under anesthesia. CONCLUSIONS: Risk stratification including genetic testing and counseling serves as the basis for screening of children at elevated risk for development of retinoblastoma.

Primary Extradural Ectopic Orbital Meningioma.

The authors describe a rare case of a primary extradural ectopic meningioma occurring in a 9-year-old female. A review of the literature with respect to clinical presentation, radiographic findings, management, and outcome among similar cases is discussed. Common features that may assist with diagnosing this unusual tumor include absence of bone or optic nerve sheath involvement, presentation at a young age, occurrence in the medial orbit, and sinus asymmetry on radiographic imaging. Preferred method of treatment is complete surgical excision.

Chronic medical conditions in adult survivors of retinoblastoma: Results of the Retinoblastoma Survivor Study.

BACKGROUND: Limited data are available regarding long-term morbidity in adult survivors of retinoblastoma (Rb). METHODS: The Retinoblastoma Survivor Study is a retrospective cohort of adult survivors of Rb diagnosed between 1932 and 1994. Participants completed a comprehensive questionnaire adapted from the Childhood Cancer Survivor Study surveys. Chronic conditions were classified using the National Cancer Institute's Common Terminology Criteria for Adverse Events (version 4.03). Multivariate Poisson regression was used to compare survivors of Rb with 2377 non-Rb controls, consisting of the Childhood Cancer Survivor Study sibling cohort and survivors with bilateral versus unilateral disease. RESULTS: Survivors of Rb (53.6% with bilateral disease) and non-Rb controls had a mean age of 43.3 years (standard deviation, 11 years) and 37.6 years (SD, 8.6 years), respectively, at the time of study enrollment. At a median follow-up of 42 years (range, 15-75 years), 86.6% of survivors of Rb had at least 1 condition and 71.1% had a severe/life-threatening (grade 3-4) condition. The adjusted relative risk (RR) of a chronic condition in survivors compared with non-Rb controls was 1.4 (95% confidence interval [95% CI], 1.3-1.4; P<.01); for a grade 3 to 4 condition, the RR was 7.6 (95% CI, 6.4-8.9; P<.01). Survivors were at an excess risk regardless of laterality. After stratifying by laterality and excluding ocular conditions and second malignant neoplasms (SMNs), only those with bilateral disease were found to be at an increased risk of any nonocular, non-SMN condition (RR, 1.2; 95% CI, 1.1-1.2) and for grade 3 to 4 nonocular, non-SMN conditions (RR, 1.7; 95% CI, 1.2-2.5). CONCLUSIONS: Survivors of Rb have an increased risk of chronic conditions compared with non-Rb controls. After excluding ocular conditions and SMNs, this excess risk was found to persist only for those with bilateral disease. Cancer 2016;122:773-781. © 2016 American Cancer Society.

Classification of Vitreous Seeds in Retinoblastoma: Correlations with Patient, Tumor, and Treatment Characteristics.

PURPOSE: To evaluate the patient, disease, and tumor characteristics of the 3 morphologically distinct groups of vitreous seeds in retinoblastoma presenting for treatment with ophthalmic artery chemosurgery (OAC): dust (class 1), spheres (class 2), and clouds (class 3) in primary and recurrent vitreous seeds. DESIGN: Retrospective cohort study of patients treated for vitreous seeds at Memorial Sloan Kettering Cancer Center between May 2006 and March 2015. PARTICIPANTS: A total of 135 eyes with active vitreous seeds, presenting for primary treatment with OAC or with recurrent vitreous disease. METHODS: Vitreous seeds were classified into 3 groups: dust, spheres, and clouds. Indirect ophthalmoscopy, fundus photography, ultrasonography, and ultrasonic biomicroscopy were used to locate and evaluate the extent of retinal and vitreous disease. Patient and disease characteristics (age, laterality of disease, treatment status) were compared among classification groups. A 2-tailed Fisher exact test and paired Student t test were used for statistical analysis. MAIN OUTCOME MEASURES: Age of patient, laterality of disease, location of retinal disease, extent of vitreous disease, and treatment status. RESULTS: Primary treated disease: Patients with eyes containing class 3 (cloud) vitreous seeds were significantly older than patients with class 1 or 2 seeds (P < 0.05). The median age of patients with class 1, 2, and 3 seeds was 11, 15.5, and 32 months, respectively. Eyes containing class 3 seeds were significantly more likely to occur in the equator-ora region of the fundus (P < 0.0001), in a diffuse pattern (P < 0.0001), and in patients with unilateral disease (P < 0.05), compared with class 1 and 2 seeds. Recurrent disease: Recurrent vitreous seeds were significantly more common to class 2 (P < 0.05), occurring in a diffuse pattern (P = 0.01) and in patients with bilateral disease (P < 0.001). CONCLUSIONS: The 3 classes of vitreous seeds have distinct clinical characteristics associated with the age of patient, laterality of disease, and extent and location of tumor-producing seeds. Furthermore, recurrent vitreous seeds appear to have a unique clinical profile compared with seeds receiving primary treatment.

The classification of vitreous seeds in retinoblastoma and response to intravitreal melphalan.

PURPOSE: To evaluate the clinical characteristics of the 3 classifications of vitreous seeds in retinoblastoma-dust (class 1), spheres (class 2), and clouds (class 3)-and their responses to intravitreal melphalan. DESIGN: Retrospective, bi-institutional cohort study. PARTICIPANTS: A total of 87 patient eyes received 475 intravitreal injections of melphalan (median dose, 30 µg) given weekly, a median of 5 times (range, 1-12 times). METHODS: At presentation, the vitreous seeds were classified into 3 groups: dust, spheres, and clouds. Indirect ophthalmoscopy, fundus photography, ultrasonography, and ultrasonic biomicroscopy were used to evaluate clinical response to weekly intravitreal melphalan injections and time to regression of vitreous seeds. Kaplan-Meier estimates of time to regression and ocular survival, patient survival, and event-free survival (EFS) were calculated and then compared using the Mantel-Cox test of curve. MAIN OUTCOME MEASURES: Time to regression of vitreous seeds, patient survival, ocular survival, and EFS. RESULTS: The difference in time to regression was significantly different for the 3 seed classes (P < 0.0001): the median time to regression was 0.6, 1.7, and 7.7 months for dust, spheres, and clouds, respectively. Eyes with dust received significantly fewer injections and a lower median and cumulative dose of melphalan, whereas eyes with clouds received significantly more injections and a higher median and cumulative dose of melphalan. Overall, the 2-year Kaplan-Meier estimates for ocular survival, patient survival, and EFS (related to target seeds) were 90.4% (95% confidence interval [CI], 79.7-95.6), 100%, and 98.5% (95% CI, 90-99.7), respectively. CONCLUSIONS: The regression and response of vitreous seeds to intravitreal melphalan are different for each seed classification. The vitreous seed classification can be predictive of time to regression, number, median dose, and cumulative dose of intravitreal melphalan injections required.

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.

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.

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.

Long-term medical outcomes in survivors of extra-ocular retinoblastoma: the Memorial Sloan-Kettering Cancer Center (MSKCC) experience.

BACKGROUND: Data on long-term outcomes of survivors of extra-ocular retinoblastoma are lacking. The authors sought to provide the first report characterizing long-term outcomes among survivors of extra-ocular retinoblastoma. PROCEDURE: Retrospective analysis of long-term medical outcomes in 19 survivors of extra-ocular retinoblastoma treated between 1992 and 2009. Severity of outcomes was graded using Common Terminology Criteria for Adverse Events. All patients received intensive multimodality therapy for their extra-ocular disease after management of their primary intra-ocular disease, including conventional chemotherapy (n = 19, 100%), radiotherapy (n = 15, 69%), and/or high-dose chemotherapy with autologous stem cell transplant (n = 17, 89%). RESULTS: The median follow-up was 7.8 years from diagnosis of extra-ocular retinoblastoma (range 2-17.8 years). The most common long-term non-visual outcomes were hearing loss (n = 15, 79%), short stature (n = 7, 37%), and secondary malignancies [SMN] (n = 6, 31%). Sixty-eight percent of survivors exhibited ≥2 non-visual long-term outcomes of any grade. Except short stature, which was not graded for severity, Grade 3-4 outcomes were limited to: ototoxicity (n = 8; n = 4 require hearing aids), SMNs (n = 6), and unequal limb length (n = 1). Five patients who developed SMNs carried a known RB1 mutation. SMNs developed at a median of 11.1 years after initial diagnosis; two patients died of their SMN. Long-term cardiac, pulmonary, hepatobiliary, or renal conditions were not identified in any survivors. CONCLUSION: Long-term outcomes are commonly seen in extra-ocular retinoblastoma survivors but the majority are mild-moderate in their severity. Longer comprehensive follow-up is needed to fully assess treatment-related outcomes but the information collected to date may affect management decisions for children with extra-ocular disease.

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.

Schimmelpenning-Feuerstein-Mims syndrome with orbital choristoma and KRAS mutation: a current review and novel case report.

INTRODUCTION: Schimmelpenning-Feurstein-Mims Syndrome (SFMS) is a rare neurocutaneous disorder. Herein, we describe a novel case and review the phenotypic spectrum and molecular findings of SFMS from an ophthalmology perspective. METHODS: Clinical case including presentation, management, pathology, and genetic analysis is described. A literature search on Schimmelpenning-Feuerstein-Mims and its synonyms, Linear nevus sebaceous syndrome, Organoid nevus syndrome, Jadassohn nevus phacomatosis, and Solomon syndrome, was conducted. An updated review and description of published cases with identified genetic mutations are described. RESULTS: A 13-year-old boy with SFMS presented with acute right eye pain and an enlarging orbital mass. Excisional biopsy of the mass revealed an orbital choristoma. Genetic analysis of the orbital tumor confirmed a KRAS c.35 G>A, p.G12D mutation. A literature search revealed 19 cases of SFMS with mutations in the RAS-pathway. KRAS, HRAS, and NRAS mutations were identified in 74%, 21%, and 5% of patients, respectively. Ophthalmic pathology was seen in 83% of patients. Systemic findings varied and involved the skin, central nervous system, and eyes most commonly. DISCUSSION: SFMS, a rare neurocutaneous disorder, results from postzygotic mosaic mutations in the RAS/MAPK pathway. Patients present with various systemic findings and ophthalmic manifestations occur in most cases. This is the first case description of a KRAS mutation identified in an orbital choristoma in SFMS. The disease is described under various names in the literature, and we propose that all syndromic cases with mosaic RAS mutations be reported under the eponym, SFMS.